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Children with HIV benefit from double dose of PCV13 vaccine

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Older HIV-infected children who have not yet receive any pneumococcal conjugate vaccine (PCV) may benefit from two doses of PCV13, while children with kidney or lung disease may need only one dose, reported Sabelle Jallow, PhD, of the University of the Witwatersrand, Johannesburg, South Africa, and associates.

An open-label study was conducted at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, South Africa, to determine the immunogenicity of one and two doses of PCV13 in vaccine-naive children with HIV infection, kidney disease, or lung disease. Of the 112 children in the study, there were 50 HIV-infected children, 8 children with kidney disease, 9 with lung disease, and 45 HIV-uninfected control children with no chronic illness. The average age at enrollment was 62 months, 53% of participants were female, and 96% were of black African descent. At-risk children were given two doses of PCV13, 2 months apart, while control children received only one PCV13 dose (Vaccine. 2017. doi: 10.1016/j.vaccine.2017.06.081).

copyright DesignPics/Thinkstock
Children who were infected with HIV or who had kidney and lung disease had similar positive responses to PCV13, compared with control children, with the exception of a few serotypes. “The at-risk children had lower [geometric mean concentrations] for serotypes 3 and 14 (except the lung disease group post-first PCV13 for serotype 14), compared to control children,” Dr. Jallow and associates said. Findings after the second PCV13 dose in both the kidney disease and lung disease groups suggested that the second dose did not have an effect. Fortunately, the responses to the initial dose appeared to be sufficient, so only one dose is likely to be required in these populations.

“In future studies, a larger spectrum of comorbidities should be included to determine the most cost-effective vaccination regimens particularly in low income countries,” the researchers noted.

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Older HIV-infected children who have not yet receive any pneumococcal conjugate vaccine (PCV) may benefit from two doses of PCV13, while children with kidney or lung disease may need only one dose, reported Sabelle Jallow, PhD, of the University of the Witwatersrand, Johannesburg, South Africa, and associates.

An open-label study was conducted at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, South Africa, to determine the immunogenicity of one and two doses of PCV13 in vaccine-naive children with HIV infection, kidney disease, or lung disease. Of the 112 children in the study, there were 50 HIV-infected children, 8 children with kidney disease, 9 with lung disease, and 45 HIV-uninfected control children with no chronic illness. The average age at enrollment was 62 months, 53% of participants were female, and 96% were of black African descent. At-risk children were given two doses of PCV13, 2 months apart, while control children received only one PCV13 dose (Vaccine. 2017. doi: 10.1016/j.vaccine.2017.06.081).

copyright DesignPics/Thinkstock
Children who were infected with HIV or who had kidney and lung disease had similar positive responses to PCV13, compared with control children, with the exception of a few serotypes. “The at-risk children had lower [geometric mean concentrations] for serotypes 3 and 14 (except the lung disease group post-first PCV13 for serotype 14), compared to control children,” Dr. Jallow and associates said. Findings after the second PCV13 dose in both the kidney disease and lung disease groups suggested that the second dose did not have an effect. Fortunately, the responses to the initial dose appeared to be sufficient, so only one dose is likely to be required in these populations.

“In future studies, a larger spectrum of comorbidities should be included to determine the most cost-effective vaccination regimens particularly in low income countries,” the researchers noted.

 

Older HIV-infected children who have not yet receive any pneumococcal conjugate vaccine (PCV) may benefit from two doses of PCV13, while children with kidney or lung disease may need only one dose, reported Sabelle Jallow, PhD, of the University of the Witwatersrand, Johannesburg, South Africa, and associates.

An open-label study was conducted at Chris Hani Baragwanath Academic Hospital (CHBAH) in Soweto, South Africa, to determine the immunogenicity of one and two doses of PCV13 in vaccine-naive children with HIV infection, kidney disease, or lung disease. Of the 112 children in the study, there were 50 HIV-infected children, 8 children with kidney disease, 9 with lung disease, and 45 HIV-uninfected control children with no chronic illness. The average age at enrollment was 62 months, 53% of participants were female, and 96% were of black African descent. At-risk children were given two doses of PCV13, 2 months apart, while control children received only one PCV13 dose (Vaccine. 2017. doi: 10.1016/j.vaccine.2017.06.081).

copyright DesignPics/Thinkstock
Children who were infected with HIV or who had kidney and lung disease had similar positive responses to PCV13, compared with control children, with the exception of a few serotypes. “The at-risk children had lower [geometric mean concentrations] for serotypes 3 and 14 (except the lung disease group post-first PCV13 for serotype 14), compared to control children,” Dr. Jallow and associates said. Findings after the second PCV13 dose in both the kidney disease and lung disease groups suggested that the second dose did not have an effect. Fortunately, the responses to the initial dose appeared to be sufficient, so only one dose is likely to be required in these populations.

“In future studies, a larger spectrum of comorbidities should be included to determine the most cost-effective vaccination regimens particularly in low income countries,” the researchers noted.

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Drug combo improves RV contractility in scleroderma-PAH

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A combination of ambrisentan (Letairis) and tadalafil (Cialis) improves regional and global right ventricular contractility in patients with scleroderma-associated pulmonary arterial hypertension, according to an open-label investigation of 23 patients.

The project was a follow-up to a previous report showing that the upfront combination – tadalafil 40 mg and ambrisentan 10 mg oral once daily – improved hemodynamics, right ventricular (RV) structure and function, and functional status in treatment-naive patients after 36 weeks and “may represent a very effective therapy for this patient population” (Am J Respir Crit Care Med. 2015 Nov 1;192(9):1102-10).

Dr. Valentina Mercurio
Survival in scleroderma pulmonary artery hypertension (PAH) depends mostly on RV function, so investigators in the follow-up study wanted to take a closer look at how the combination affected the heart. They reviewed conventional echocardiograph imaging and RV strain analyses for the 23 of the 24 patients in the original trial for which it was available (Am J Respir Crit Care Med. 2017 Jun 29. doi: 10.1164/rccm.201704-0789LE).

At baseline, the subjects had normal left ventricular (LV) size and function, with borderline left atrial enlargement and mild LV diastolic dysfunction. Their right heart chambers were significantly dilated, with RV hypertrophy. Conventional RV function parameters – tricuspid annular systolic plane excursion (TAPSE) and fractional area change (FAC) – were impaired. RV systolic pressure (RVSP) was severely elevated. There was also a marked reduction of global RV longitudinal systolic strain (RVLSS), compared with normal values mainly because of a reduction in midventricular and apical RVLSS, with relative hyperkinesis of basal RVLSS

After 36 weeks of treatment, right heart chamber sizes were significantly reduced. There was also a decrease in RV free wall thickness, which coincided with a significant reduction in RV mass on cardiac MRI. TAPSE, FAC, and global RVLSS improved significantly, and RVSP decreased significantly. LV end-diastolic and end-systolic diameters and volumes increased significantly.

The changes “may represent transition from maladaptive RV remodeling ... to a more physiological and adaptive RV remodeling;” however, “the effects of treatment should be interpreted with caution, as this was an open-label study without a placebo or a single-drug control group,” said investigators led by Valentina Mercurio, MD, a postdoc fellow at Johns Hopkins University, Baltimore.

“It is conceivable that a heterogeneous RVLSS pattern exists in [scleroderma] patients with longitudinal hyperkinetic basal segment as the predominant vector of contraction early in the disease course. As PAH develops, the ability of the basal segment to compensate decreases, and RV failure ensues, suggesting a ‘two-hit’ hypothesis, in which a preexisting RV contractile dysfunction may predispose to further RV impairment when a second insult (PAH development) occurs,” they said.

Subjects were about 60 years old on average, and most were women. The majority shifted from World Health Organization PAH functional class 3 to 2 during the original trial. Mean 6 minute walk tests increased from 341 m to 401 m.

Gilead and United Therapeutics provided the ambrisentan and tadalafil. Dr. Mercurio reported funding from both companies and Merck. The original study was sponsored by United Therapeutics.
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Dr. Jason Lazar
Dual therapy is standard therapy for PAH but not for secondary pulmonary hypertension. Dual oral therapy represents a novel approach for treatment, and very few studies have demonstrated any drug to benefit secondary pulmonary hypertension.
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Dr. Jason Lazar
Dual therapy is standard therapy for PAH but not for secondary pulmonary hypertension. Dual oral therapy represents a novel approach for treatment, and very few studies have demonstrated any drug to benefit secondary pulmonary hypertension.
Body

Dr. Jason Lazar
Dual therapy is standard therapy for PAH but not for secondary pulmonary hypertension. Dual oral therapy represents a novel approach for treatment, and very few studies have demonstrated any drug to benefit secondary pulmonary hypertension.
Title
Comment by Jason Lazar, MD, FCCP
Comment by Jason Lazar, MD, FCCP

 

A combination of ambrisentan (Letairis) and tadalafil (Cialis) improves regional and global right ventricular contractility in patients with scleroderma-associated pulmonary arterial hypertension, according to an open-label investigation of 23 patients.

The project was a follow-up to a previous report showing that the upfront combination – tadalafil 40 mg and ambrisentan 10 mg oral once daily – improved hemodynamics, right ventricular (RV) structure and function, and functional status in treatment-naive patients after 36 weeks and “may represent a very effective therapy for this patient population” (Am J Respir Crit Care Med. 2015 Nov 1;192(9):1102-10).

Dr. Valentina Mercurio
Survival in scleroderma pulmonary artery hypertension (PAH) depends mostly on RV function, so investigators in the follow-up study wanted to take a closer look at how the combination affected the heart. They reviewed conventional echocardiograph imaging and RV strain analyses for the 23 of the 24 patients in the original trial for which it was available (Am J Respir Crit Care Med. 2017 Jun 29. doi: 10.1164/rccm.201704-0789LE).

At baseline, the subjects had normal left ventricular (LV) size and function, with borderline left atrial enlargement and mild LV diastolic dysfunction. Their right heart chambers were significantly dilated, with RV hypertrophy. Conventional RV function parameters – tricuspid annular systolic plane excursion (TAPSE) and fractional area change (FAC) – were impaired. RV systolic pressure (RVSP) was severely elevated. There was also a marked reduction of global RV longitudinal systolic strain (RVLSS), compared with normal values mainly because of a reduction in midventricular and apical RVLSS, with relative hyperkinesis of basal RVLSS

After 36 weeks of treatment, right heart chamber sizes were significantly reduced. There was also a decrease in RV free wall thickness, which coincided with a significant reduction in RV mass on cardiac MRI. TAPSE, FAC, and global RVLSS improved significantly, and RVSP decreased significantly. LV end-diastolic and end-systolic diameters and volumes increased significantly.

The changes “may represent transition from maladaptive RV remodeling ... to a more physiological and adaptive RV remodeling;” however, “the effects of treatment should be interpreted with caution, as this was an open-label study without a placebo or a single-drug control group,” said investigators led by Valentina Mercurio, MD, a postdoc fellow at Johns Hopkins University, Baltimore.

“It is conceivable that a heterogeneous RVLSS pattern exists in [scleroderma] patients with longitudinal hyperkinetic basal segment as the predominant vector of contraction early in the disease course. As PAH develops, the ability of the basal segment to compensate decreases, and RV failure ensues, suggesting a ‘two-hit’ hypothesis, in which a preexisting RV contractile dysfunction may predispose to further RV impairment when a second insult (PAH development) occurs,” they said.

Subjects were about 60 years old on average, and most were women. The majority shifted from World Health Organization PAH functional class 3 to 2 during the original trial. Mean 6 minute walk tests increased from 341 m to 401 m.

Gilead and United Therapeutics provided the ambrisentan and tadalafil. Dr. Mercurio reported funding from both companies and Merck. The original study was sponsored by United Therapeutics.

 

A combination of ambrisentan (Letairis) and tadalafil (Cialis) improves regional and global right ventricular contractility in patients with scleroderma-associated pulmonary arterial hypertension, according to an open-label investigation of 23 patients.

The project was a follow-up to a previous report showing that the upfront combination – tadalafil 40 mg and ambrisentan 10 mg oral once daily – improved hemodynamics, right ventricular (RV) structure and function, and functional status in treatment-naive patients after 36 weeks and “may represent a very effective therapy for this patient population” (Am J Respir Crit Care Med. 2015 Nov 1;192(9):1102-10).

Dr. Valentina Mercurio
Survival in scleroderma pulmonary artery hypertension (PAH) depends mostly on RV function, so investigators in the follow-up study wanted to take a closer look at how the combination affected the heart. They reviewed conventional echocardiograph imaging and RV strain analyses for the 23 of the 24 patients in the original trial for which it was available (Am J Respir Crit Care Med. 2017 Jun 29. doi: 10.1164/rccm.201704-0789LE).

At baseline, the subjects had normal left ventricular (LV) size and function, with borderline left atrial enlargement and mild LV diastolic dysfunction. Their right heart chambers were significantly dilated, with RV hypertrophy. Conventional RV function parameters – tricuspid annular systolic plane excursion (TAPSE) and fractional area change (FAC) – were impaired. RV systolic pressure (RVSP) was severely elevated. There was also a marked reduction of global RV longitudinal systolic strain (RVLSS), compared with normal values mainly because of a reduction in midventricular and apical RVLSS, with relative hyperkinesis of basal RVLSS

After 36 weeks of treatment, right heart chamber sizes were significantly reduced. There was also a decrease in RV free wall thickness, which coincided with a significant reduction in RV mass on cardiac MRI. TAPSE, FAC, and global RVLSS improved significantly, and RVSP decreased significantly. LV end-diastolic and end-systolic diameters and volumes increased significantly.

The changes “may represent transition from maladaptive RV remodeling ... to a more physiological and adaptive RV remodeling;” however, “the effects of treatment should be interpreted with caution, as this was an open-label study without a placebo or a single-drug control group,” said investigators led by Valentina Mercurio, MD, a postdoc fellow at Johns Hopkins University, Baltimore.

“It is conceivable that a heterogeneous RVLSS pattern exists in [scleroderma] patients with longitudinal hyperkinetic basal segment as the predominant vector of contraction early in the disease course. As PAH develops, the ability of the basal segment to compensate decreases, and RV failure ensues, suggesting a ‘two-hit’ hypothesis, in which a preexisting RV contractile dysfunction may predispose to further RV impairment when a second insult (PAH development) occurs,” they said.

Subjects were about 60 years old on average, and most were women. The majority shifted from World Health Organization PAH functional class 3 to 2 during the original trial. Mean 6 minute walk tests increased from 341 m to 401 m.

Gilead and United Therapeutics provided the ambrisentan and tadalafil. Dr. Mercurio reported funding from both companies and Merck. The original study was sponsored by United Therapeutics.
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FROM THE AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE

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Key clinical point: A combination of ambrisentan (Letairis) and tadalafil (Cialis) improves regional and global right ventricular contractility in patients with scleroderma-associated pulmonary arterial hypertension.

Major finding: After 36 weeks of treatment, TAPSE, FAC, and global RVLSS improved significantly, and RV systolic pressure decreased significantly.

Data source: Cardiac imaging of 23 patients.

Disclosures: Gilead and United Therapeutics provided the ambrisentan and tadalafil. The lead investigator reported funding from both companies and Merck. The original study was sponsored by United Therapeutics.

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Algorithm for identifying IPF has low PPV

Case validation is key
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ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy, according to Kaiser Permanente and University of California, San Francisco (UCSF), investigators.

“In the age of large administrative databases and electronic medical records, there is rich opportunity to conduct population-based studies” of disease behavior, outcomes, health care use, and other matters, but researchers first need to be able to accurately identify patients with idiopathic pulmonary fibrosis (IPF) in large data sets, said investigators led by Brett Ley, MD, an assistant professor of medicine at UCSF.

The research community has traditionally relied on claims for specific IPF diagnostic codes – ICD-9 code 516.3 or ICD-9-CM code 516.31 – to identify patients, but the approach had never been validated. To see how well it works, the investigators applied it to the nearly 5.4 million adults in the Kaiser Permanente Northern California system during 2000-2014. After patients with interstitial lung disease-associated codes entered on or after the day of the last IPF code were excluded, the algorithm identified 2,608 patients as having IPF (Ann Am Thorac Soc. 2017 Jun;14[6]:880-7).

Next, the investigators randomly selected 150 of those patients and examined their medical records, procedure codes, CTs, and other patient-level data to see how many of them really had IPF. The results weren’t good. The positive predictive value of the IPF code-based algorithm was only 42.2%, with a sensitivity 55.6%.

The widely used code-based IPF algorithm does “not generate accurate estimates of IPF incidence and prevalence. ... Over half of the patients identified as having IPF ... did not have IPF on case review. Alarmingly, whereas half of the misclassified cases had an alternative [interstitial lung disease] diagnosis, the other half had no clinical or radiologic evidence of ILD [interstitial lung disease] at all.” The algorithm also “likely misses a substantial proportion of patients who do have IPF,” Dr. Ley and his colleagues said.

“We can only speculate about the reasons. ... It seems likely to be due to a combination of misdiagnosis at the clinical level and miscoding at the administrative level,” they said.

To try to improve the situation, the team tweaked the algorithm to include only patients 50 years or older who had at least two 516.3 or 516.31 claims 1 month or more apart and a chest CT procedure code beforehand. They again excluded ILD-associated claims on or after the day of the last IPF code.

Although the sensitivity of the modified algorithm was lower than the original, it had a more robust positive predictive value of 70.4% in the derivation cohort and 61.8% in the validation cohort, both derived from the 150 patients used to validate the original algorithm.

“By making a few simple, empirically derived changes to the IPF algorithm,” it’s possible to “more reliably identif[y] patients” with IPF. “We believe the modified IPF algorithm will be useful for population-based studies of IPF ... that require high diagnostic certainty,” the investigators concluded.

The traditional algorithm found an incidence of 6.8 cases per 100,000 person-years, which was on the low end of previous reports, perhaps because of the relative health and youth of the 5.4 million patient pool. As in past studies, IPF incidence increased with older age and was highest in white patients and men.

“Whether the more specific codes provided by the ICD-10 system will allow for improved case classification of IPF requires further study,” the investigators noted.

The work was funded by the National Institutes of Health. Dr. Ley reported speaker’s fees from Genentech, and one of the authors was an employee of the company. The senior author Harold Collard, MD, an associate professor in UCSF’s Division of Pulmonary and Critical Care Medicine, reported personal fees from Takeda, ImmuneWorks, Parexel, Pharma Capital Partners, and others.
 

Body

 

This study glaringly displays potential problems with using ICD codes for research purposes and calls into question results from a handful of studies that yielded epidemiological estimates for idiopathic pulmonary fibrosis. We are reminded that practitioner-generated diagnostic codes of IPF recorded in the medical record are subject to inaccuracies, which can be illuminated by the “gold standard” – multidisciplinary adjudication.

Moving forward, particularly as longitudinal, nationwide IPF registries come online, patient-level case validation should be employed. As we move into the era of ICD-10, the study should serve as a call to improve IPF case ascertainment accuracy for any investigators choosing to use large data analytic strategies. Doing so will mute the background noise and allow us to better hear the signals of this complex disease.

Evans R. Fernandez Perez, MD, is a pulmonologist at National Jewish Health, Denver. He made his comments in an editorial, and reported speaker’s fees from Boehringer Ingelheim and Genentech (Ann Am Thorac Soc. 2017 Jun;14[6]:829-30).

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This study glaringly displays potential problems with using ICD codes for research purposes and calls into question results from a handful of studies that yielded epidemiological estimates for idiopathic pulmonary fibrosis. We are reminded that practitioner-generated diagnostic codes of IPF recorded in the medical record are subject to inaccuracies, which can be illuminated by the “gold standard” – multidisciplinary adjudication.

Moving forward, particularly as longitudinal, nationwide IPF registries come online, patient-level case validation should be employed. As we move into the era of ICD-10, the study should serve as a call to improve IPF case ascertainment accuracy for any investigators choosing to use large data analytic strategies. Doing so will mute the background noise and allow us to better hear the signals of this complex disease.

Evans R. Fernandez Perez, MD, is a pulmonologist at National Jewish Health, Denver. He made his comments in an editorial, and reported speaker’s fees from Boehringer Ingelheim and Genentech (Ann Am Thorac Soc. 2017 Jun;14[6]:829-30).

Body

 

This study glaringly displays potential problems with using ICD codes for research purposes and calls into question results from a handful of studies that yielded epidemiological estimates for idiopathic pulmonary fibrosis. We are reminded that practitioner-generated diagnostic codes of IPF recorded in the medical record are subject to inaccuracies, which can be illuminated by the “gold standard” – multidisciplinary adjudication.

Moving forward, particularly as longitudinal, nationwide IPF registries come online, patient-level case validation should be employed. As we move into the era of ICD-10, the study should serve as a call to improve IPF case ascertainment accuracy for any investigators choosing to use large data analytic strategies. Doing so will mute the background noise and allow us to better hear the signals of this complex disease.

Evans R. Fernandez Perez, MD, is a pulmonologist at National Jewish Health, Denver. He made his comments in an editorial, and reported speaker’s fees from Boehringer Ingelheim and Genentech (Ann Am Thorac Soc. 2017 Jun;14[6]:829-30).

Title
Case validation is key
Case validation is key

 

ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy, according to Kaiser Permanente and University of California, San Francisco (UCSF), investigators.

“In the age of large administrative databases and electronic medical records, there is rich opportunity to conduct population-based studies” of disease behavior, outcomes, health care use, and other matters, but researchers first need to be able to accurately identify patients with idiopathic pulmonary fibrosis (IPF) in large data sets, said investigators led by Brett Ley, MD, an assistant professor of medicine at UCSF.

The research community has traditionally relied on claims for specific IPF diagnostic codes – ICD-9 code 516.3 or ICD-9-CM code 516.31 – to identify patients, but the approach had never been validated. To see how well it works, the investigators applied it to the nearly 5.4 million adults in the Kaiser Permanente Northern California system during 2000-2014. After patients with interstitial lung disease-associated codes entered on or after the day of the last IPF code were excluded, the algorithm identified 2,608 patients as having IPF (Ann Am Thorac Soc. 2017 Jun;14[6]:880-7).

Next, the investigators randomly selected 150 of those patients and examined their medical records, procedure codes, CTs, and other patient-level data to see how many of them really had IPF. The results weren’t good. The positive predictive value of the IPF code-based algorithm was only 42.2%, with a sensitivity 55.6%.

The widely used code-based IPF algorithm does “not generate accurate estimates of IPF incidence and prevalence. ... Over half of the patients identified as having IPF ... did not have IPF on case review. Alarmingly, whereas half of the misclassified cases had an alternative [interstitial lung disease] diagnosis, the other half had no clinical or radiologic evidence of ILD [interstitial lung disease] at all.” The algorithm also “likely misses a substantial proportion of patients who do have IPF,” Dr. Ley and his colleagues said.

“We can only speculate about the reasons. ... It seems likely to be due to a combination of misdiagnosis at the clinical level and miscoding at the administrative level,” they said.

To try to improve the situation, the team tweaked the algorithm to include only patients 50 years or older who had at least two 516.3 or 516.31 claims 1 month or more apart and a chest CT procedure code beforehand. They again excluded ILD-associated claims on or after the day of the last IPF code.

Although the sensitivity of the modified algorithm was lower than the original, it had a more robust positive predictive value of 70.4% in the derivation cohort and 61.8% in the validation cohort, both derived from the 150 patients used to validate the original algorithm.

“By making a few simple, empirically derived changes to the IPF algorithm,” it’s possible to “more reliably identif[y] patients” with IPF. “We believe the modified IPF algorithm will be useful for population-based studies of IPF ... that require high diagnostic certainty,” the investigators concluded.

The traditional algorithm found an incidence of 6.8 cases per 100,000 person-years, which was on the low end of previous reports, perhaps because of the relative health and youth of the 5.4 million patient pool. As in past studies, IPF incidence increased with older age and was highest in white patients and men.

“Whether the more specific codes provided by the ICD-10 system will allow for improved case classification of IPF requires further study,” the investigators noted.

The work was funded by the National Institutes of Health. Dr. Ley reported speaker’s fees from Genentech, and one of the authors was an employee of the company. The senior author Harold Collard, MD, an associate professor in UCSF’s Division of Pulmonary and Critical Care Medicine, reported personal fees from Takeda, ImmuneWorks, Parexel, Pharma Capital Partners, and others.
 

 

ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy, according to Kaiser Permanente and University of California, San Francisco (UCSF), investigators.

“In the age of large administrative databases and electronic medical records, there is rich opportunity to conduct population-based studies” of disease behavior, outcomes, health care use, and other matters, but researchers first need to be able to accurately identify patients with idiopathic pulmonary fibrosis (IPF) in large data sets, said investigators led by Brett Ley, MD, an assistant professor of medicine at UCSF.

The research community has traditionally relied on claims for specific IPF diagnostic codes – ICD-9 code 516.3 or ICD-9-CM code 516.31 – to identify patients, but the approach had never been validated. To see how well it works, the investigators applied it to the nearly 5.4 million adults in the Kaiser Permanente Northern California system during 2000-2014. After patients with interstitial lung disease-associated codes entered on or after the day of the last IPF code were excluded, the algorithm identified 2,608 patients as having IPF (Ann Am Thorac Soc. 2017 Jun;14[6]:880-7).

Next, the investigators randomly selected 150 of those patients and examined their medical records, procedure codes, CTs, and other patient-level data to see how many of them really had IPF. The results weren’t good. The positive predictive value of the IPF code-based algorithm was only 42.2%, with a sensitivity 55.6%.

The widely used code-based IPF algorithm does “not generate accurate estimates of IPF incidence and prevalence. ... Over half of the patients identified as having IPF ... did not have IPF on case review. Alarmingly, whereas half of the misclassified cases had an alternative [interstitial lung disease] diagnosis, the other half had no clinical or radiologic evidence of ILD [interstitial lung disease] at all.” The algorithm also “likely misses a substantial proportion of patients who do have IPF,” Dr. Ley and his colleagues said.

“We can only speculate about the reasons. ... It seems likely to be due to a combination of misdiagnosis at the clinical level and miscoding at the administrative level,” they said.

To try to improve the situation, the team tweaked the algorithm to include only patients 50 years or older who had at least two 516.3 or 516.31 claims 1 month or more apart and a chest CT procedure code beforehand. They again excluded ILD-associated claims on or after the day of the last IPF code.

Although the sensitivity of the modified algorithm was lower than the original, it had a more robust positive predictive value of 70.4% in the derivation cohort and 61.8% in the validation cohort, both derived from the 150 patients used to validate the original algorithm.

“By making a few simple, empirically derived changes to the IPF algorithm,” it’s possible to “more reliably identif[y] patients” with IPF. “We believe the modified IPF algorithm will be useful for population-based studies of IPF ... that require high diagnostic certainty,” the investigators concluded.

The traditional algorithm found an incidence of 6.8 cases per 100,000 person-years, which was on the low end of previous reports, perhaps because of the relative health and youth of the 5.4 million patient pool. As in past studies, IPF incidence increased with older age and was highest in white patients and men.

“Whether the more specific codes provided by the ICD-10 system will allow for improved case classification of IPF requires further study,” the investigators noted.

The work was funded by the National Institutes of Health. Dr. Ley reported speaker’s fees from Genentech, and one of the authors was an employee of the company. The senior author Harold Collard, MD, an associate professor in UCSF’s Division of Pulmonary and Critical Care Medicine, reported personal fees from Takeda, ImmuneWorks, Parexel, Pharma Capital Partners, and others.
 

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FROM THE ANNALS OF THE AMERICAN THORACIC SOCIETY

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Key clinical point: ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy.

Major finding: The positive predictive value of the traditional IPF code-based algorithm was only 42.2%, with a sensitivity of 55.6%.

Data source: A study including almost 5.4 million patients at Kaiser Permanente Northern California.

Disclosures: The work was funded by the National Institutes of Health. One of the investigators was a Genentech employee. Others reported speaker’s and personal fees from Genentech and other companies.

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Do sleep interventions prevent atrial fibrillation?

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– If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?

Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.

Dr. Reena Mehra
Results from several retrospective studies all show that, in patients with atrial fibrillation who undergo cardioversion or ablation, those who also have OSA and are treated for their OSA are less likely to have recurrent atrial fibrillation than are patients who are not treated for their OSA. “This has been shown consistently,” with relative risks reduced two- to fourfold in atrial fibrillation patients treated with CPAP, compared with similar, untreated patients, Reena Mehra, MD, a pulmonologist and director of sleep disorders research at the Cleveland Clinic, said in an interview during an international conference of the American Thoracic Society.

Dr. Olaf Oldenburg
“The success of pulmonary vein isolation [for resolving atrial fibrillation] is highly influenced by OSA. You can improve the success of pulmonary vein isolation if you treat OSA patients with CPAP. That’s an established benefit,” agreed Olaf Oldenburg, MD, a cardiologist and sleep disorders physician at the Heart and Diabetes Center of Ruhr University in Bad Oeynhausen, Germany. Dr. Oldenburg also agreed that the application of this approach in routine practice has been very spotty.

“Only a very small number of patients with atrial fibrillation undergo a sleep study,” he said in an interview. “Before I’d send my mother for atrial fibrillation ablation, I would first look for sleep disordered breathing [SDB],” but this generally isn’t happening routinely. Patients with other types of cardiovascular disease who could potentially benefit from sleep disordered breathing diagnosis and treatment are those with hypertension, especially patients who don’t fully respond to three or more antihypertensive drugs and patients with heart failure with preserved ejection fraction, he added.

Dr. Oldenburg also echoed Dr. Mehra in saying that the evidence supporting this approach for managing atrial fibrillation is less than conclusive.

“We need more precise phenotyping of patients” to better focus on patients with cardiovascular disease and sleep disordered breathing who clearly benefit from CPAP intervention, he said.

Results from the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, reported in September 2016, especially tarnished the notion that treating sleep disordered breathing in patients with various cardiovascular diseases can help avoid future cardiovascular events. The multicenter trial enrolled 2,717 adults with moderate to severe obstructive sleep apnea and cardiovascular disease to receive either CPAP plus optimal routine care or optimal routine care only. After an average follow-up of close to 4 years, the patients treated with CPAP showed no benefit in terms of reduced cardiovascular events (N Engl J Med. 2016 Sept 8;375[10]:919-31).

An editorial that ran with this report suggested that the neutral outcome may have occurred because the average nightly duration of CPAP that patients in the trial self administered was just over 3 hours, arguably an inadequate dose. Other possible reasons for the lack of benefit include the time during their sleep cycle when patients administered CPAP (at the start of sleep rather than later) and that CPAP may have a reduced ability to avert new cardiovascular events in patients with established cardiovascular disease (N Engl J Med. 2016 Sept 8;375[8]:994-6).

Regardless of the reasons, the SAVE results, coupled with the neutral results and suggestion of harm from using adaptive servo-ventilation in patients with heart failure with reduced ejection fraction and central sleep apnea in the SERVE-HF trial (N Engl J Med. 2015 Sept 17;373[12]:1095-105), have thrust the management of SDB in patients with cardiovascular disease back to the point where SDB interventions have no well-proven indications for cardiovascular disease patients.

“With the SERVE-HF and SAVE trials not showing benefit, we now have equipoise” for using or not using SDB interventions in these patients, Dr. Mehra said. “It’s not clear that treating OSA improves outcomes. That allows us to randomize patients to a control placebo arm” in future trials.

An important issue in the failure to clearly establish a role for treating OSA in patients with atrial fibrillation or other cardiovascular diseases may have been over reliance on the apnea-hypopnea index (AHI) as the arbiter of OSA severity, Dr. Oldenburg said. “Maybe there are parameters to look at aside from AHI, perhaps hypoxemia burden or desaturation time. AHI is not the whole truth; we need to look at other parameters. AHI may not be the correct metric to look at in patients with various cardiovascular diseases.”

Dr. Tetyana Kendzerska
The superiority of other measures for gauging SDB severity was reinforced by new results reported at the meeting. A review of more than 8,000 patients who were free from any heart arrhythmia and who underwent a sleep study at the University of Toronto during 1994-2010 identified 173 who subsequently developed atrial fibrillation. Analysis of the sleep study findings showed that no cut point for AHI, even a rate of more than 30 sleep disruptions an hour, was significantly linked with later onset of atrial fibrillation, reported Tetyana Kendzerska, MD, a sleep researcher at the the Ottawa Hospital Research Institute. However, when evaluated by the amount of time that patients spent asleep with an oxygen saturation level of less than 90%, those with this level of hypoxemia during at least 30% of their sleep had a 2.5-fold higher rate of later hospitalization for atrial fibrillation, compared with the patients with a lesser burden of nocturnal hypoxemia, in a model that adjusted for several baseline demographic and clinical differences, Dr. Kendzerska said. Among the 8,256 patients she reviewed, 6% fell into this group, with meaningful oxygen desaturation during more than 30% of their time asleep.

Her analysis also showed that patients with at least 10 minutes of sleep time with an oxygen saturation rate of 90% or less had a 64% increased rate of later atrial fibrillation hospitalizations, compared with those with fewer than 10 minutes spent in this state. Nearly a quarter of the patients studied fell into this category.

“Nocturnal oxygen desaturation may be stronger than AHI for predicting atrial fibrillation development,” Dr. Kendzerska concluded. “The severity of OSA-related intermittent hypoxia may be more important than sleep fragmentation in the development of atrial fibrillation. These findings support a relationship between OSA, chronic nocturnal hypoxemia, and new onset atrial fibrillation.”

However, using oxygen desaturation instead of AHI to gauge the severity of OSA won’t solve all the challenges that sleep researchers currently face in trying to determine the efficacy of breathing interventions to prevent or treat cardiovascular disease. In the neutral SAVE trial, researchers used nocturnal oxygen saturation levels to select patients with clinically meaningful OSA.

Dr. Mehra and Dr. Kendzerska had no disclosures. Dr. Oldenburg has received consultant fees, honoraria, and/or research support from ResMed, Respicardia, and Weinmann.
 

 

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– If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?

Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.

Dr. Reena Mehra
Results from several retrospective studies all show that, in patients with atrial fibrillation who undergo cardioversion or ablation, those who also have OSA and are treated for their OSA are less likely to have recurrent atrial fibrillation than are patients who are not treated for their OSA. “This has been shown consistently,” with relative risks reduced two- to fourfold in atrial fibrillation patients treated with CPAP, compared with similar, untreated patients, Reena Mehra, MD, a pulmonologist and director of sleep disorders research at the Cleveland Clinic, said in an interview during an international conference of the American Thoracic Society.

Dr. Olaf Oldenburg
“The success of pulmonary vein isolation [for resolving atrial fibrillation] is highly influenced by OSA. You can improve the success of pulmonary vein isolation if you treat OSA patients with CPAP. That’s an established benefit,” agreed Olaf Oldenburg, MD, a cardiologist and sleep disorders physician at the Heart and Diabetes Center of Ruhr University in Bad Oeynhausen, Germany. Dr. Oldenburg also agreed that the application of this approach in routine practice has been very spotty.

“Only a very small number of patients with atrial fibrillation undergo a sleep study,” he said in an interview. “Before I’d send my mother for atrial fibrillation ablation, I would first look for sleep disordered breathing [SDB],” but this generally isn’t happening routinely. Patients with other types of cardiovascular disease who could potentially benefit from sleep disordered breathing diagnosis and treatment are those with hypertension, especially patients who don’t fully respond to three or more antihypertensive drugs and patients with heart failure with preserved ejection fraction, he added.

Dr. Oldenburg also echoed Dr. Mehra in saying that the evidence supporting this approach for managing atrial fibrillation is less than conclusive.

“We need more precise phenotyping of patients” to better focus on patients with cardiovascular disease and sleep disordered breathing who clearly benefit from CPAP intervention, he said.

Results from the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, reported in September 2016, especially tarnished the notion that treating sleep disordered breathing in patients with various cardiovascular diseases can help avoid future cardiovascular events. The multicenter trial enrolled 2,717 adults with moderate to severe obstructive sleep apnea and cardiovascular disease to receive either CPAP plus optimal routine care or optimal routine care only. After an average follow-up of close to 4 years, the patients treated with CPAP showed no benefit in terms of reduced cardiovascular events (N Engl J Med. 2016 Sept 8;375[10]:919-31).

An editorial that ran with this report suggested that the neutral outcome may have occurred because the average nightly duration of CPAP that patients in the trial self administered was just over 3 hours, arguably an inadequate dose. Other possible reasons for the lack of benefit include the time during their sleep cycle when patients administered CPAP (at the start of sleep rather than later) and that CPAP may have a reduced ability to avert new cardiovascular events in patients with established cardiovascular disease (N Engl J Med. 2016 Sept 8;375[8]:994-6).

Regardless of the reasons, the SAVE results, coupled with the neutral results and suggestion of harm from using adaptive servo-ventilation in patients with heart failure with reduced ejection fraction and central sleep apnea in the SERVE-HF trial (N Engl J Med. 2015 Sept 17;373[12]:1095-105), have thrust the management of SDB in patients with cardiovascular disease back to the point where SDB interventions have no well-proven indications for cardiovascular disease patients.

“With the SERVE-HF and SAVE trials not showing benefit, we now have equipoise” for using or not using SDB interventions in these patients, Dr. Mehra said. “It’s not clear that treating OSA improves outcomes. That allows us to randomize patients to a control placebo arm” in future trials.

An important issue in the failure to clearly establish a role for treating OSA in patients with atrial fibrillation or other cardiovascular diseases may have been over reliance on the apnea-hypopnea index (AHI) as the arbiter of OSA severity, Dr. Oldenburg said. “Maybe there are parameters to look at aside from AHI, perhaps hypoxemia burden or desaturation time. AHI is not the whole truth; we need to look at other parameters. AHI may not be the correct metric to look at in patients with various cardiovascular diseases.”

Dr. Tetyana Kendzerska
The superiority of other measures for gauging SDB severity was reinforced by new results reported at the meeting. A review of more than 8,000 patients who were free from any heart arrhythmia and who underwent a sleep study at the University of Toronto during 1994-2010 identified 173 who subsequently developed atrial fibrillation. Analysis of the sleep study findings showed that no cut point for AHI, even a rate of more than 30 sleep disruptions an hour, was significantly linked with later onset of atrial fibrillation, reported Tetyana Kendzerska, MD, a sleep researcher at the the Ottawa Hospital Research Institute. However, when evaluated by the amount of time that patients spent asleep with an oxygen saturation level of less than 90%, those with this level of hypoxemia during at least 30% of their sleep had a 2.5-fold higher rate of later hospitalization for atrial fibrillation, compared with the patients with a lesser burden of nocturnal hypoxemia, in a model that adjusted for several baseline demographic and clinical differences, Dr. Kendzerska said. Among the 8,256 patients she reviewed, 6% fell into this group, with meaningful oxygen desaturation during more than 30% of their time asleep.

Her analysis also showed that patients with at least 10 minutes of sleep time with an oxygen saturation rate of 90% or less had a 64% increased rate of later atrial fibrillation hospitalizations, compared with those with fewer than 10 minutes spent in this state. Nearly a quarter of the patients studied fell into this category.

“Nocturnal oxygen desaturation may be stronger than AHI for predicting atrial fibrillation development,” Dr. Kendzerska concluded. “The severity of OSA-related intermittent hypoxia may be more important than sleep fragmentation in the development of atrial fibrillation. These findings support a relationship between OSA, chronic nocturnal hypoxemia, and new onset atrial fibrillation.”

However, using oxygen desaturation instead of AHI to gauge the severity of OSA won’t solve all the challenges that sleep researchers currently face in trying to determine the efficacy of breathing interventions to prevent or treat cardiovascular disease. In the neutral SAVE trial, researchers used nocturnal oxygen saturation levels to select patients with clinically meaningful OSA.

Dr. Mehra and Dr. Kendzerska had no disclosures. Dr. Oldenburg has received consultant fees, honoraria, and/or research support from ResMed, Respicardia, and Weinmann.
 

 

 

– If patients have sleep disordered breathing with obstructive sleep apnea, will its treatment have cardiovascular disease benefits, especially in terms of the incidence or severity of atrial fibrillation?

Observational evidence suggests that apnea interventions may help these patients, but no clear case yet exists to prove that a breathing intervention works, experts say, and, as a result, U.S. practice is mixed when it comes to using treatment for obstructive sleep apnea (OSA), specifically continuous positive airway pressure (CPAP), to prevent or treat atrial fibrillation.

Dr. Reena Mehra
Results from several retrospective studies all show that, in patients with atrial fibrillation who undergo cardioversion or ablation, those who also have OSA and are treated for their OSA are less likely to have recurrent atrial fibrillation than are patients who are not treated for their OSA. “This has been shown consistently,” with relative risks reduced two- to fourfold in atrial fibrillation patients treated with CPAP, compared with similar, untreated patients, Reena Mehra, MD, a pulmonologist and director of sleep disorders research at the Cleveland Clinic, said in an interview during an international conference of the American Thoracic Society.

Dr. Olaf Oldenburg
“The success of pulmonary vein isolation [for resolving atrial fibrillation] is highly influenced by OSA. You can improve the success of pulmonary vein isolation if you treat OSA patients with CPAP. That’s an established benefit,” agreed Olaf Oldenburg, MD, a cardiologist and sleep disorders physician at the Heart and Diabetes Center of Ruhr University in Bad Oeynhausen, Germany. Dr. Oldenburg also agreed that the application of this approach in routine practice has been very spotty.

“Only a very small number of patients with atrial fibrillation undergo a sleep study,” he said in an interview. “Before I’d send my mother for atrial fibrillation ablation, I would first look for sleep disordered breathing [SDB],” but this generally isn’t happening routinely. Patients with other types of cardiovascular disease who could potentially benefit from sleep disordered breathing diagnosis and treatment are those with hypertension, especially patients who don’t fully respond to three or more antihypertensive drugs and patients with heart failure with preserved ejection fraction, he added.

Dr. Oldenburg also echoed Dr. Mehra in saying that the evidence supporting this approach for managing atrial fibrillation is less than conclusive.

“We need more precise phenotyping of patients” to better focus on patients with cardiovascular disease and sleep disordered breathing who clearly benefit from CPAP intervention, he said.

Results from the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, reported in September 2016, especially tarnished the notion that treating sleep disordered breathing in patients with various cardiovascular diseases can help avoid future cardiovascular events. The multicenter trial enrolled 2,717 adults with moderate to severe obstructive sleep apnea and cardiovascular disease to receive either CPAP plus optimal routine care or optimal routine care only. After an average follow-up of close to 4 years, the patients treated with CPAP showed no benefit in terms of reduced cardiovascular events (N Engl J Med. 2016 Sept 8;375[10]:919-31).

An editorial that ran with this report suggested that the neutral outcome may have occurred because the average nightly duration of CPAP that patients in the trial self administered was just over 3 hours, arguably an inadequate dose. Other possible reasons for the lack of benefit include the time during their sleep cycle when patients administered CPAP (at the start of sleep rather than later) and that CPAP may have a reduced ability to avert new cardiovascular events in patients with established cardiovascular disease (N Engl J Med. 2016 Sept 8;375[8]:994-6).

Regardless of the reasons, the SAVE results, coupled with the neutral results and suggestion of harm from using adaptive servo-ventilation in patients with heart failure with reduced ejection fraction and central sleep apnea in the SERVE-HF trial (N Engl J Med. 2015 Sept 17;373[12]:1095-105), have thrust the management of SDB in patients with cardiovascular disease back to the point where SDB interventions have no well-proven indications for cardiovascular disease patients.

“With the SERVE-HF and SAVE trials not showing benefit, we now have equipoise” for using or not using SDB interventions in these patients, Dr. Mehra said. “It’s not clear that treating OSA improves outcomes. That allows us to randomize patients to a control placebo arm” in future trials.

An important issue in the failure to clearly establish a role for treating OSA in patients with atrial fibrillation or other cardiovascular diseases may have been over reliance on the apnea-hypopnea index (AHI) as the arbiter of OSA severity, Dr. Oldenburg said. “Maybe there are parameters to look at aside from AHI, perhaps hypoxemia burden or desaturation time. AHI is not the whole truth; we need to look at other parameters. AHI may not be the correct metric to look at in patients with various cardiovascular diseases.”

Dr. Tetyana Kendzerska
The superiority of other measures for gauging SDB severity was reinforced by new results reported at the meeting. A review of more than 8,000 patients who were free from any heart arrhythmia and who underwent a sleep study at the University of Toronto during 1994-2010 identified 173 who subsequently developed atrial fibrillation. Analysis of the sleep study findings showed that no cut point for AHI, even a rate of more than 30 sleep disruptions an hour, was significantly linked with later onset of atrial fibrillation, reported Tetyana Kendzerska, MD, a sleep researcher at the the Ottawa Hospital Research Institute. However, when evaluated by the amount of time that patients spent asleep with an oxygen saturation level of less than 90%, those with this level of hypoxemia during at least 30% of their sleep had a 2.5-fold higher rate of later hospitalization for atrial fibrillation, compared with the patients with a lesser burden of nocturnal hypoxemia, in a model that adjusted for several baseline demographic and clinical differences, Dr. Kendzerska said. Among the 8,256 patients she reviewed, 6% fell into this group, with meaningful oxygen desaturation during more than 30% of their time asleep.

Her analysis also showed that patients with at least 10 minutes of sleep time with an oxygen saturation rate of 90% or less had a 64% increased rate of later atrial fibrillation hospitalizations, compared with those with fewer than 10 minutes spent in this state. Nearly a quarter of the patients studied fell into this category.

“Nocturnal oxygen desaturation may be stronger than AHI for predicting atrial fibrillation development,” Dr. Kendzerska concluded. “The severity of OSA-related intermittent hypoxia may be more important than sleep fragmentation in the development of atrial fibrillation. These findings support a relationship between OSA, chronic nocturnal hypoxemia, and new onset atrial fibrillation.”

However, using oxygen desaturation instead of AHI to gauge the severity of OSA won’t solve all the challenges that sleep researchers currently face in trying to determine the efficacy of breathing interventions to prevent or treat cardiovascular disease. In the neutral SAVE trial, researchers used nocturnal oxygen saturation levels to select patients with clinically meaningful OSA.

Dr. Mehra and Dr. Kendzerska had no disclosures. Dr. Oldenburg has received consultant fees, honoraria, and/or research support from ResMed, Respicardia, and Weinmann.
 

 

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TB meningitis cases in U.S. are fewer but more complicated

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– The number of cases of meningitis caused by tuberculosis has fallen dramatically in the United States in recent decades as TB itself has become less common, according to findings from a study presented at the annual meeting of the American Academy of Neurology.

However, these findings from patient hospitalizations during 1993-2013 in the Nationwide Inpatient Sample database also indicate that neurologic complications from TB meningitis are on the rise.

The findings suggest that neurologists need to become involved whenever a patient with TB shows signs of neurologic problems, said study lead author Alexander E. Merkler, MD, of Cornell University, New York, in an interview. “They’re at high risk, and some complications can be life threatening.”

Zerbor/Thinkstock
In 2013, the Handbook of Clinical Neurology stated that TB meningitis “is common in resource-poor communities but also occurs in developed countries where the diagnosis is frequently delayed because of unfamiliarity with the disease” (Handb Clin Neurol. 2013;112:1135-8). Its burden is especially large in Africa, where a 2014 report said it remains of “significant public health importance with a very high fatality, which has remained stagnant for the past half-century” (J Neurol. 2014 May;261[5]:851-65).

According to Dr. Merkler, TB meningitis occurs when a patient’s case of TB invades the meninges surrounding the brain. “It can lead to seizures, stroke, hydrocephalus, and death,” he said at the meeting.

TB meningitis can affect anyone with TB, he said, but those who are immunocompromised and those with diabetes are especially vulnerable.

For their current study, Dr. Merkler and his associates used the Nationwide Inpatient Sample database to track patients hospitalized in the United States with TB meningitis from 1993 to 2013. They found 16,196 new cases over the 20-year period and uncovered a dramatic decrease in the rate of hospitalizations: The incidence fell from 6.2 to 1.9 hospitalizations per million people (rate difference, 4.3; 95% confidence interval, 2.1-6.5; P less than .001), and mortality during index hospitalization fell from 17.6% (95% CI, 12.0%-23.2%) to 7.6%, (95% CI, 2.2%-13.0%).

Dr. Merkler said that mortality appears to have declined as TB itself has become less common. According to the Centers for Disease Control and Prevention, the number of reported TB cases nationally was 9,557 in 2015, a rate of 3.0 cases per 100,000 persons. The total number of annual cases fell each year from 1993 to 2014, the CDC reported, although the rate leveled off at around 3.0/100,000 from 2013 to 2015.

“The fewer people have lung TB, the less they’ll have it going into meningitis and the brain,” Dr. Merkler said. “In terms of mortality, it is going down because we have better supportive care. We’re better at keeping these patients alive and giving them antibiotics sooner.”

However, the study found that the rates of the following complications in hospitalized TB meningitis patients rose over the 20-year period:
 

• Hydrocephalus, from 2.3% (95% confidence interval, 0.5%-4.2%) to 5.4% (95% CI, 2.3%-10.0%).

• Seizure, from 2.9% (95% CI, 0.3%-5.4%) to 14.1% (95% CI, 7.3%-21.0%).

• Stroke, from 2.9% (95% CI, 0.6%-5.3%) to 13.0% (95% CI, 6.3%-19.8%).

• Vision and hearing impairment, from 8.2% (95% CI, 4.8%-11.6%) to 10.9% (95% CI, 4.1%-17.6%), and from 1.1% (95% CI, 0.0%-2.3%) to 3.3% (95% CI, 0.0%-6.9%), respectively.

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– The number of cases of meningitis caused by tuberculosis has fallen dramatically in the United States in recent decades as TB itself has become less common, according to findings from a study presented at the annual meeting of the American Academy of Neurology.

However, these findings from patient hospitalizations during 1993-2013 in the Nationwide Inpatient Sample database also indicate that neurologic complications from TB meningitis are on the rise.

The findings suggest that neurologists need to become involved whenever a patient with TB shows signs of neurologic problems, said study lead author Alexander E. Merkler, MD, of Cornell University, New York, in an interview. “They’re at high risk, and some complications can be life threatening.”

Zerbor/Thinkstock
In 2013, the Handbook of Clinical Neurology stated that TB meningitis “is common in resource-poor communities but also occurs in developed countries where the diagnosis is frequently delayed because of unfamiliarity with the disease” (Handb Clin Neurol. 2013;112:1135-8). Its burden is especially large in Africa, where a 2014 report said it remains of “significant public health importance with a very high fatality, which has remained stagnant for the past half-century” (J Neurol. 2014 May;261[5]:851-65).

According to Dr. Merkler, TB meningitis occurs when a patient’s case of TB invades the meninges surrounding the brain. “It can lead to seizures, stroke, hydrocephalus, and death,” he said at the meeting.

TB meningitis can affect anyone with TB, he said, but those who are immunocompromised and those with diabetes are especially vulnerable.

For their current study, Dr. Merkler and his associates used the Nationwide Inpatient Sample database to track patients hospitalized in the United States with TB meningitis from 1993 to 2013. They found 16,196 new cases over the 20-year period and uncovered a dramatic decrease in the rate of hospitalizations: The incidence fell from 6.2 to 1.9 hospitalizations per million people (rate difference, 4.3; 95% confidence interval, 2.1-6.5; P less than .001), and mortality during index hospitalization fell from 17.6% (95% CI, 12.0%-23.2%) to 7.6%, (95% CI, 2.2%-13.0%).

Dr. Merkler said that mortality appears to have declined as TB itself has become less common. According to the Centers for Disease Control and Prevention, the number of reported TB cases nationally was 9,557 in 2015, a rate of 3.0 cases per 100,000 persons. The total number of annual cases fell each year from 1993 to 2014, the CDC reported, although the rate leveled off at around 3.0/100,000 from 2013 to 2015.

“The fewer people have lung TB, the less they’ll have it going into meningitis and the brain,” Dr. Merkler said. “In terms of mortality, it is going down because we have better supportive care. We’re better at keeping these patients alive and giving them antibiotics sooner.”

However, the study found that the rates of the following complications in hospitalized TB meningitis patients rose over the 20-year period:
 

• Hydrocephalus, from 2.3% (95% confidence interval, 0.5%-4.2%) to 5.4% (95% CI, 2.3%-10.0%).

• Seizure, from 2.9% (95% CI, 0.3%-5.4%) to 14.1% (95% CI, 7.3%-21.0%).

• Stroke, from 2.9% (95% CI, 0.6%-5.3%) to 13.0% (95% CI, 6.3%-19.8%).

• Vision and hearing impairment, from 8.2% (95% CI, 4.8%-11.6%) to 10.9% (95% CI, 4.1%-17.6%), and from 1.1% (95% CI, 0.0%-2.3%) to 3.3% (95% CI, 0.0%-6.9%), respectively.

 

– The number of cases of meningitis caused by tuberculosis has fallen dramatically in the United States in recent decades as TB itself has become less common, according to findings from a study presented at the annual meeting of the American Academy of Neurology.

However, these findings from patient hospitalizations during 1993-2013 in the Nationwide Inpatient Sample database also indicate that neurologic complications from TB meningitis are on the rise.

The findings suggest that neurologists need to become involved whenever a patient with TB shows signs of neurologic problems, said study lead author Alexander E. Merkler, MD, of Cornell University, New York, in an interview. “They’re at high risk, and some complications can be life threatening.”

Zerbor/Thinkstock
In 2013, the Handbook of Clinical Neurology stated that TB meningitis “is common in resource-poor communities but also occurs in developed countries where the diagnosis is frequently delayed because of unfamiliarity with the disease” (Handb Clin Neurol. 2013;112:1135-8). Its burden is especially large in Africa, where a 2014 report said it remains of “significant public health importance with a very high fatality, which has remained stagnant for the past half-century” (J Neurol. 2014 May;261[5]:851-65).

According to Dr. Merkler, TB meningitis occurs when a patient’s case of TB invades the meninges surrounding the brain. “It can lead to seizures, stroke, hydrocephalus, and death,” he said at the meeting.

TB meningitis can affect anyone with TB, he said, but those who are immunocompromised and those with diabetes are especially vulnerable.

For their current study, Dr. Merkler and his associates used the Nationwide Inpatient Sample database to track patients hospitalized in the United States with TB meningitis from 1993 to 2013. They found 16,196 new cases over the 20-year period and uncovered a dramatic decrease in the rate of hospitalizations: The incidence fell from 6.2 to 1.9 hospitalizations per million people (rate difference, 4.3; 95% confidence interval, 2.1-6.5; P less than .001), and mortality during index hospitalization fell from 17.6% (95% CI, 12.0%-23.2%) to 7.6%, (95% CI, 2.2%-13.0%).

Dr. Merkler said that mortality appears to have declined as TB itself has become less common. According to the Centers for Disease Control and Prevention, the number of reported TB cases nationally was 9,557 in 2015, a rate of 3.0 cases per 100,000 persons. The total number of annual cases fell each year from 1993 to 2014, the CDC reported, although the rate leveled off at around 3.0/100,000 from 2013 to 2015.

“The fewer people have lung TB, the less they’ll have it going into meningitis and the brain,” Dr. Merkler said. “In terms of mortality, it is going down because we have better supportive care. We’re better at keeping these patients alive and giving them antibiotics sooner.”

However, the study found that the rates of the following complications in hospitalized TB meningitis patients rose over the 20-year period:
 

• Hydrocephalus, from 2.3% (95% confidence interval, 0.5%-4.2%) to 5.4% (95% CI, 2.3%-10.0%).

• Seizure, from 2.9% (95% CI, 0.3%-5.4%) to 14.1% (95% CI, 7.3%-21.0%).

• Stroke, from 2.9% (95% CI, 0.6%-5.3%) to 13.0% (95% CI, 6.3%-19.8%).

• Vision and hearing impairment, from 8.2% (95% CI, 4.8%-11.6%) to 10.9% (95% CI, 4.1%-17.6%), and from 1.1% (95% CI, 0.0%-2.3%) to 3.3% (95% CI, 0.0%-6.9%), respectively.

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Key clinical point: The number of tuberculous meningitis cases in the United States declined dramatically over 2 decades, as did mortality, but complication rates have risen.

Major finding: The rate of TB meningitis hospitalizations fell from 6.2 to 1.9 per million people (rate difference, 4.3; 95% CI, 2.1-6.5; P less than .001).

Data source: The Nationwide Inpatient Sample database, which revealed 16,196 new cases of TB meningitis from 1993 to 2013.

Disclosures: The study was funded by the National Institute of Neurological Disorders and Stroke and the Michael Goldberg Stroke Research Fund. Dr. Merkler reported no relevant financial disclosures.

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Nurses help more rheumatic disease patients get vaccinated

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– A nurse-led program successfully increased the uptake of pneumococcal vaccination among patients with chronic inflammatory rheumatic diseases in a single-center study.

From the start to the end of a 4-month evaluation period, the rate of vaccination of at-risk patients increased from 17.1% (13/76) to 77.6% (59/76; P less than .001).

Sara Freeman/Frontline Medical News
Dr. Tiphaine Goulenok
The findings show that a simple intervention, involving a nurse’s assessment of patients’ eligibility, led to a discussion between a nurse and patient about the benefits and risks of being vaccinated and of not being vaccinated. The study also demonstrated that having a nurse administer the vaccine can have a dramatic effect on how many patients agree to be vaccinated for pneumococcal disease.

It is well known that patients with inflammatory rheumatic diseases, such as systemic lupus erythematous (SLE) and systemic vasculitis, are at high risk for contracting pneumococcal disease, reported Tiphaine Goulenok, MD, of Bichat Hospital, Paris, at the European Congress of Rheumatology. This is particularly the case if they are receiving immunosuppressive treatments.

Although French national guidelines were introduced in 2011 that recommend that such patients routinely receive pneumococcal vaccination, the vaccination rate is often lower than is desirable, Dr. Goulenok observed at a press briefing. Her prior research suggests that only 16.2% of patients with an indication for the PCV13 vaccine actually received it.

In the current study, 126 patients with inflammatory rheumatic diseases were consecutively recruited and seen at the day unit of Bichat Hospital. Of these patients, 76 were candidates for pneumococcal vaccination because they were receiving steroids or other immunosuppressive drugs. Of these patients, 13 were already vaccinated, and, of the 63 who were not, nurses correctly identified 56 (88.9%) who needed to be vaccinated, of whom 46 agreed and 10 refused.

“We found a low rate of pneumococcal vaccination among patients,” said Dr. Goulenok, “but, thanks to high screening by the nurses, vaccination coverage was increased and the nurse-led vaccination program was very efficient”.

Robert Landewé, MD, who chaired the press briefing, observed that, despite being in an “era of guidelines,” ways of successfully implementing them in practice remained a challenge. The nurse-led program appeared to be one way to increase pneumococcal vaccination uptake, but perhaps other ways need to be sought, especially as there may be substantial resistance to vaccination among patients, he said.

“Patients are sometimes more afraid of the consequences of vaccination than [of] the disease that is prevented by vaccination,” said Dr. Landewé, who is professor of rheumatology at the Academic Medical Center in Amsterdam (the Netherlands).

Dr. Goulenok and Dr. Landewé reported no disclosures.
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– A nurse-led program successfully increased the uptake of pneumococcal vaccination among patients with chronic inflammatory rheumatic diseases in a single-center study.

From the start to the end of a 4-month evaluation period, the rate of vaccination of at-risk patients increased from 17.1% (13/76) to 77.6% (59/76; P less than .001).

Sara Freeman/Frontline Medical News
Dr. Tiphaine Goulenok
The findings show that a simple intervention, involving a nurse’s assessment of patients’ eligibility, led to a discussion between a nurse and patient about the benefits and risks of being vaccinated and of not being vaccinated. The study also demonstrated that having a nurse administer the vaccine can have a dramatic effect on how many patients agree to be vaccinated for pneumococcal disease.

It is well known that patients with inflammatory rheumatic diseases, such as systemic lupus erythematous (SLE) and systemic vasculitis, are at high risk for contracting pneumococcal disease, reported Tiphaine Goulenok, MD, of Bichat Hospital, Paris, at the European Congress of Rheumatology. This is particularly the case if they are receiving immunosuppressive treatments.

Although French national guidelines were introduced in 2011 that recommend that such patients routinely receive pneumococcal vaccination, the vaccination rate is often lower than is desirable, Dr. Goulenok observed at a press briefing. Her prior research suggests that only 16.2% of patients with an indication for the PCV13 vaccine actually received it.

In the current study, 126 patients with inflammatory rheumatic diseases were consecutively recruited and seen at the day unit of Bichat Hospital. Of these patients, 76 were candidates for pneumococcal vaccination because they were receiving steroids or other immunosuppressive drugs. Of these patients, 13 were already vaccinated, and, of the 63 who were not, nurses correctly identified 56 (88.9%) who needed to be vaccinated, of whom 46 agreed and 10 refused.

“We found a low rate of pneumococcal vaccination among patients,” said Dr. Goulenok, “but, thanks to high screening by the nurses, vaccination coverage was increased and the nurse-led vaccination program was very efficient”.

Robert Landewé, MD, who chaired the press briefing, observed that, despite being in an “era of guidelines,” ways of successfully implementing them in practice remained a challenge. The nurse-led program appeared to be one way to increase pneumococcal vaccination uptake, but perhaps other ways need to be sought, especially as there may be substantial resistance to vaccination among patients, he said.

“Patients are sometimes more afraid of the consequences of vaccination than [of] the disease that is prevented by vaccination,” said Dr. Landewé, who is professor of rheumatology at the Academic Medical Center in Amsterdam (the Netherlands).

Dr. Goulenok and Dr. Landewé reported no disclosures.

 

– A nurse-led program successfully increased the uptake of pneumococcal vaccination among patients with chronic inflammatory rheumatic diseases in a single-center study.

From the start to the end of a 4-month evaluation period, the rate of vaccination of at-risk patients increased from 17.1% (13/76) to 77.6% (59/76; P less than .001).

Sara Freeman/Frontline Medical News
Dr. Tiphaine Goulenok
The findings show that a simple intervention, involving a nurse’s assessment of patients’ eligibility, led to a discussion between a nurse and patient about the benefits and risks of being vaccinated and of not being vaccinated. The study also demonstrated that having a nurse administer the vaccine can have a dramatic effect on how many patients agree to be vaccinated for pneumococcal disease.

It is well known that patients with inflammatory rheumatic diseases, such as systemic lupus erythematous (SLE) and systemic vasculitis, are at high risk for contracting pneumococcal disease, reported Tiphaine Goulenok, MD, of Bichat Hospital, Paris, at the European Congress of Rheumatology. This is particularly the case if they are receiving immunosuppressive treatments.

Although French national guidelines were introduced in 2011 that recommend that such patients routinely receive pneumococcal vaccination, the vaccination rate is often lower than is desirable, Dr. Goulenok observed at a press briefing. Her prior research suggests that only 16.2% of patients with an indication for the PCV13 vaccine actually received it.

In the current study, 126 patients with inflammatory rheumatic diseases were consecutively recruited and seen at the day unit of Bichat Hospital. Of these patients, 76 were candidates for pneumococcal vaccination because they were receiving steroids or other immunosuppressive drugs. Of these patients, 13 were already vaccinated, and, of the 63 who were not, nurses correctly identified 56 (88.9%) who needed to be vaccinated, of whom 46 agreed and 10 refused.

“We found a low rate of pneumococcal vaccination among patients,” said Dr. Goulenok, “but, thanks to high screening by the nurses, vaccination coverage was increased and the nurse-led vaccination program was very efficient”.

Robert Landewé, MD, who chaired the press briefing, observed that, despite being in an “era of guidelines,” ways of successfully implementing them in practice remained a challenge. The nurse-led program appeared to be one way to increase pneumococcal vaccination uptake, but perhaps other ways need to be sought, especially as there may be substantial resistance to vaccination among patients, he said.

“Patients are sometimes more afraid of the consequences of vaccination than [of] the disease that is prevented by vaccination,” said Dr. Landewé, who is professor of rheumatology at the Academic Medical Center in Amsterdam (the Netherlands).

Dr. Goulenok and Dr. Landewé reported no disclosures.
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Key clinical point: A nurse-led program increased the uptake of a guideline-recommended vaccination in patients with chronic inflammatory rheumatic diseases.

Major finding: The pre- and postintervention pneumococcal vaccination rates were 17.1% (13/76) and 77.6% (59/76) of at-risk patients (P less than .001).

Data source: A 4-month, prospective pilot study of 126 consecutively recruited patients with chronic inflammatory rheumatic diseases.

Disclosures: The presenter and commentator had no disclosures to report.

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FDA approves betrixaban for VTE prophylaxis

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Betrixaban, a factor Xa inhibitor, has been approved for the prophylaxis of venous thromboembolism (VTE) in at-risk adult patients hospitalized with an acute illness, according to an announcement from the Food and Drug Administration.

Approval was based on results from a randomized, double-blind clinical trial in which over 7,000 hospitalized patients at risk for VTE received either extended-duration betrixaban (35-42 days) or short duration enoxaparin (6-14 days), a low molecular weight heparin administered subcutaneously. The rate of deep vein thrombosis, nonfatal pulmonary embolism, or VTE-related death was 4.4% among patients receiving betrixaban and 6% among patients receiving enoxaparin (relative risk, 0.75; 95% confidence interval: 0.61, 0.91).

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License
A total of 54% of patients receiving betrixaban had at least one adverse event, compared with 52% of patients receiving enoxaparin. The incidence of serious adverse events was also similar for both groups at 18% among betrixaban-treated patients and 17% among enoxaparin-treated patients. The most common adverse events were related to bleeding (2.4% for betrixaban and 1.2% for enoxaparin), which was also the most common reason for treatment discontinuation in both groups.

The recommended dosage for betrixaban is 80 mg per day for 35-42 days at the same time every day with food, after a dose of 160 mg on the first day of treatment.

Betrixaban will be marketed as Bevyxxa by Portola.

Find the full FDA announcement and prescribing information on the FDA website.

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Betrixaban, a factor Xa inhibitor, has been approved for the prophylaxis of venous thromboembolism (VTE) in at-risk adult patients hospitalized with an acute illness, according to an announcement from the Food and Drug Administration.

Approval was based on results from a randomized, double-blind clinical trial in which over 7,000 hospitalized patients at risk for VTE received either extended-duration betrixaban (35-42 days) or short duration enoxaparin (6-14 days), a low molecular weight heparin administered subcutaneously. The rate of deep vein thrombosis, nonfatal pulmonary embolism, or VTE-related death was 4.4% among patients receiving betrixaban and 6% among patients receiving enoxaparin (relative risk, 0.75; 95% confidence interval: 0.61, 0.91).

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License
A total of 54% of patients receiving betrixaban had at least one adverse event, compared with 52% of patients receiving enoxaparin. The incidence of serious adverse events was also similar for both groups at 18% among betrixaban-treated patients and 17% among enoxaparin-treated patients. The most common adverse events were related to bleeding (2.4% for betrixaban and 1.2% for enoxaparin), which was also the most common reason for treatment discontinuation in both groups.

The recommended dosage for betrixaban is 80 mg per day for 35-42 days at the same time every day with food, after a dose of 160 mg on the first day of treatment.

Betrixaban will be marketed as Bevyxxa by Portola.

Find the full FDA announcement and prescribing information on the FDA website.

 

Betrixaban, a factor Xa inhibitor, has been approved for the prophylaxis of venous thromboembolism (VTE) in at-risk adult patients hospitalized with an acute illness, according to an announcement from the Food and Drug Administration.

Approval was based on results from a randomized, double-blind clinical trial in which over 7,000 hospitalized patients at risk for VTE received either extended-duration betrixaban (35-42 days) or short duration enoxaparin (6-14 days), a low molecular weight heparin administered subcutaneously. The rate of deep vein thrombosis, nonfatal pulmonary embolism, or VTE-related death was 4.4% among patients receiving betrixaban and 6% among patients receiving enoxaparin (relative risk, 0.75; 95% confidence interval: 0.61, 0.91).

Courtesy Wikimedia Commons/FitzColinGerald/Creative Commons License
A total of 54% of patients receiving betrixaban had at least one adverse event, compared with 52% of patients receiving enoxaparin. The incidence of serious adverse events was also similar for both groups at 18% among betrixaban-treated patients and 17% among enoxaparin-treated patients. The most common adverse events were related to bleeding (2.4% for betrixaban and 1.2% for enoxaparin), which was also the most common reason for treatment discontinuation in both groups.

The recommended dosage for betrixaban is 80 mg per day for 35-42 days at the same time every day with food, after a dose of 160 mg on the first day of treatment.

Betrixaban will be marketed as Bevyxxa by Portola.

Find the full FDA announcement and prescribing information on the FDA website.

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ACIP approves new influenza vaccine recommendations

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FROM AN ACIP MEETING

New draft recommendations on influenza vaccines for children and pregnant women were unanimously passed by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) after a lengthy debate over specifics regarding recommendations for pregnant women.

The proposed recommendation that sparked the debate would change the wording of the previous recommendation for pregnant women to receive a seasonal inactivated vaccine (IIV) to “any licensed, recommended, and age-appropriate, trivalent or quadrivalent IIV or RIV [recombinant influenza vaccine] may be used.”

Steve Mann/Thinkstock
Members of the committee were hesitant to introduce this new wording, concerned that the language was too strong for the uncertainty some of the committee felt about the safety of including a recombinant influenza vaccine (RIV), Flublok, among those recommended.

“I think there’s a subtle, but important difference here between making what would appear to be an affirmative statement that RIV is safe in pregnant women, versus just staying silent on it, and saying ‘we’re not saying you shouldn’t use it, but we don’t have enough data to affirmatively say it is safe,’ ” said Cindy Pellegrini, senior vice president of Public Policy and Government Affairs at the March of Dimes Foundation.

In response, members of the committee pointed out that the responsibility of determining safety lies with the Food and Drug Administration, which has already licensed the Flublok trivalent vaccine with expectations that the quadrivalent vaccine soon will follow.

While Lisa Grohskopf, MD, MPH, medical officer of the influenza division of the CDC, did acknowledge that there were more data on the safety of inactivated influenza vaccines, she asserted to the committee that “the general overall safety profile of Flublok in comparison to inactivated vaccines is reassuring.”

“For example, one concern that arises is reactogenicity and inflammation. [In terms of] overall reactogenicity in the studies where Flublok and inactivated vaccines have been compared, rates of the adverse and systemic reactions were similar,” Dr. Grohskopf said.

A motion was made to change the wording of the recommendation; however, the motion was not passed, and the eventual vote on the approval was conducted.

The ACIP also voted unanimously to change the safe age limit noted in influenza guidelines for use of Afluria (IIV3) from 9 years and older to 5 years and older. A footnote saying that the ACIP recommends Afluria for children 9 years and older will be removed.

This change, which mirrors the licensing Afluria has with the FDA, was based on research conducted by Seqirus that showed fever levels were the same for Afluria trivalent and quadrivalent vaccines in children 5 to 9 years old, both of which were less than historical vaccine rates.

The approved recommendations will be sent to the director of the CDC and the U.S. Department of Health and Human Services. Once reviewed and approved, the final recommendations will be published in the CDC’s Morbidity and Mortality Weekly Report. The committee members had no relevant financial disclosures.

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FROM AN ACIP MEETING

New draft recommendations on influenza vaccines for children and pregnant women were unanimously passed by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) after a lengthy debate over specifics regarding recommendations for pregnant women.

The proposed recommendation that sparked the debate would change the wording of the previous recommendation for pregnant women to receive a seasonal inactivated vaccine (IIV) to “any licensed, recommended, and age-appropriate, trivalent or quadrivalent IIV or RIV [recombinant influenza vaccine] may be used.”

Steve Mann/Thinkstock
Members of the committee were hesitant to introduce this new wording, concerned that the language was too strong for the uncertainty some of the committee felt about the safety of including a recombinant influenza vaccine (RIV), Flublok, among those recommended.

“I think there’s a subtle, but important difference here between making what would appear to be an affirmative statement that RIV is safe in pregnant women, versus just staying silent on it, and saying ‘we’re not saying you shouldn’t use it, but we don’t have enough data to affirmatively say it is safe,’ ” said Cindy Pellegrini, senior vice president of Public Policy and Government Affairs at the March of Dimes Foundation.

In response, members of the committee pointed out that the responsibility of determining safety lies with the Food and Drug Administration, which has already licensed the Flublok trivalent vaccine with expectations that the quadrivalent vaccine soon will follow.

While Lisa Grohskopf, MD, MPH, medical officer of the influenza division of the CDC, did acknowledge that there were more data on the safety of inactivated influenza vaccines, she asserted to the committee that “the general overall safety profile of Flublok in comparison to inactivated vaccines is reassuring.”

“For example, one concern that arises is reactogenicity and inflammation. [In terms of] overall reactogenicity in the studies where Flublok and inactivated vaccines have been compared, rates of the adverse and systemic reactions were similar,” Dr. Grohskopf said.

A motion was made to change the wording of the recommendation; however, the motion was not passed, and the eventual vote on the approval was conducted.

The ACIP also voted unanimously to change the safe age limit noted in influenza guidelines for use of Afluria (IIV3) from 9 years and older to 5 years and older. A footnote saying that the ACIP recommends Afluria for children 9 years and older will be removed.

This change, which mirrors the licensing Afluria has with the FDA, was based on research conducted by Seqirus that showed fever levels were the same for Afluria trivalent and quadrivalent vaccines in children 5 to 9 years old, both of which were less than historical vaccine rates.

The approved recommendations will be sent to the director of the CDC and the U.S. Department of Health and Human Services. Once reviewed and approved, the final recommendations will be published in the CDC’s Morbidity and Mortality Weekly Report. The committee members had no relevant financial disclosures.

 

FROM AN ACIP MEETING

New draft recommendations on influenza vaccines for children and pregnant women were unanimously passed by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) after a lengthy debate over specifics regarding recommendations for pregnant women.

The proposed recommendation that sparked the debate would change the wording of the previous recommendation for pregnant women to receive a seasonal inactivated vaccine (IIV) to “any licensed, recommended, and age-appropriate, trivalent or quadrivalent IIV or RIV [recombinant influenza vaccine] may be used.”

Steve Mann/Thinkstock
Members of the committee were hesitant to introduce this new wording, concerned that the language was too strong for the uncertainty some of the committee felt about the safety of including a recombinant influenza vaccine (RIV), Flublok, among those recommended.

“I think there’s a subtle, but important difference here between making what would appear to be an affirmative statement that RIV is safe in pregnant women, versus just staying silent on it, and saying ‘we’re not saying you shouldn’t use it, but we don’t have enough data to affirmatively say it is safe,’ ” said Cindy Pellegrini, senior vice president of Public Policy and Government Affairs at the March of Dimes Foundation.

In response, members of the committee pointed out that the responsibility of determining safety lies with the Food and Drug Administration, which has already licensed the Flublok trivalent vaccine with expectations that the quadrivalent vaccine soon will follow.

While Lisa Grohskopf, MD, MPH, medical officer of the influenza division of the CDC, did acknowledge that there were more data on the safety of inactivated influenza vaccines, she asserted to the committee that “the general overall safety profile of Flublok in comparison to inactivated vaccines is reassuring.”

“For example, one concern that arises is reactogenicity and inflammation. [In terms of] overall reactogenicity in the studies where Flublok and inactivated vaccines have been compared, rates of the adverse and systemic reactions were similar,” Dr. Grohskopf said.

A motion was made to change the wording of the recommendation; however, the motion was not passed, and the eventual vote on the approval was conducted.

The ACIP also voted unanimously to change the safe age limit noted in influenza guidelines for use of Afluria (IIV3) from 9 years and older to 5 years and older. A footnote saying that the ACIP recommends Afluria for children 9 years and older will be removed.

This change, which mirrors the licensing Afluria has with the FDA, was based on research conducted by Seqirus that showed fever levels were the same for Afluria trivalent and quadrivalent vaccines in children 5 to 9 years old, both of which were less than historical vaccine rates.

The approved recommendations will be sent to the director of the CDC and the U.S. Department of Health and Human Services. Once reviewed and approved, the final recommendations will be published in the CDC’s Morbidity and Mortality Weekly Report. The committee members had no relevant financial disclosures.

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Tipoffs that an infant hospitalized with pertussis may require ICU

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– Infants hospitalized for pertussis are more likely to develop severe disease requiring pediatric ICU admission if they are experiencing apnea, are unvaccinated against pertussis, or are less than 2 months old, Maria Arranz, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

“The presence of these parameters on admission should warn us of possible severe disease,” said Dr. Arranz of Gregorio Maranon Hospital in Madrid.

Dr. Maria Arranz
Also, infants with severe pertussis develop significantly higher peak levels of leukocytes, lymphocytes, and neutrophils during their hospital stay, although not necessarily on admission, she added.

Dr. Arranz presented a retrospective observational study of 101 children under 1 year of age who were hospitalized for pertussis at the Madrid tertiary center prior to the hospital’s 2016 shift to a strategy of maternal immunization during pregnancy as a means of preventing pertussis in infancy. Thirteen percent of the children required admission to the pediatric ICU and thus by definition had severe disease.

Half of infants in the study were not vaccinated against pertussis. That proved to be a powerful risk factor for severe disease requiring an ICU stay. Only 8% of children with severe pertussis were vaccinated, compared with a 58% vaccination rate among those who avoided the ICU.

Apneic pauses were noted in 67% of the severe disease group, compared with 28% of the infants who didn’t need the ICU.

The pertussis patients admitted to the pediatric ICU averaged 1 month of age, compared with age 2 months in the nonsevere group.

The maximum leukocyte, lymphocyte, and neutrophil counts during the hospital stay of the severe disease group averaged 23,600 cells/mm3, 18,000/mm3, and 5,000/mm3, respectively, significantly greater than the 15,300, 10,700, and 3,900 cells/mm3 in infants who did not require the ICU. Levels of all three cells also were higher at admission in the severe pertussis group than in those who didn’t make it to the ICU, albeit not statistically significantly so.

Dr. Arranz reported having no financial conflicts of interest regarding her study.
 
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– Infants hospitalized for pertussis are more likely to develop severe disease requiring pediatric ICU admission if they are experiencing apnea, are unvaccinated against pertussis, or are less than 2 months old, Maria Arranz, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

“The presence of these parameters on admission should warn us of possible severe disease,” said Dr. Arranz of Gregorio Maranon Hospital in Madrid.

Dr. Maria Arranz
Also, infants with severe pertussis develop significantly higher peak levels of leukocytes, lymphocytes, and neutrophils during their hospital stay, although not necessarily on admission, she added.

Dr. Arranz presented a retrospective observational study of 101 children under 1 year of age who were hospitalized for pertussis at the Madrid tertiary center prior to the hospital’s 2016 shift to a strategy of maternal immunization during pregnancy as a means of preventing pertussis in infancy. Thirteen percent of the children required admission to the pediatric ICU and thus by definition had severe disease.

Half of infants in the study were not vaccinated against pertussis. That proved to be a powerful risk factor for severe disease requiring an ICU stay. Only 8% of children with severe pertussis were vaccinated, compared with a 58% vaccination rate among those who avoided the ICU.

Apneic pauses were noted in 67% of the severe disease group, compared with 28% of the infants who didn’t need the ICU.

The pertussis patients admitted to the pediatric ICU averaged 1 month of age, compared with age 2 months in the nonsevere group.

The maximum leukocyte, lymphocyte, and neutrophil counts during the hospital stay of the severe disease group averaged 23,600 cells/mm3, 18,000/mm3, and 5,000/mm3, respectively, significantly greater than the 15,300, 10,700, and 3,900 cells/mm3 in infants who did not require the ICU. Levels of all three cells also were higher at admission in the severe pertussis group than in those who didn’t make it to the ICU, albeit not statistically significantly so.

Dr. Arranz reported having no financial conflicts of interest regarding her study.
 

 

– Infants hospitalized for pertussis are more likely to develop severe disease requiring pediatric ICU admission if they are experiencing apnea, are unvaccinated against pertussis, or are less than 2 months old, Maria Arranz, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.

“The presence of these parameters on admission should warn us of possible severe disease,” said Dr. Arranz of Gregorio Maranon Hospital in Madrid.

Dr. Maria Arranz
Also, infants with severe pertussis develop significantly higher peak levels of leukocytes, lymphocytes, and neutrophils during their hospital stay, although not necessarily on admission, she added.

Dr. Arranz presented a retrospective observational study of 101 children under 1 year of age who were hospitalized for pertussis at the Madrid tertiary center prior to the hospital’s 2016 shift to a strategy of maternal immunization during pregnancy as a means of preventing pertussis in infancy. Thirteen percent of the children required admission to the pediatric ICU and thus by definition had severe disease.

Half of infants in the study were not vaccinated against pertussis. That proved to be a powerful risk factor for severe disease requiring an ICU stay. Only 8% of children with severe pertussis were vaccinated, compared with a 58% vaccination rate among those who avoided the ICU.

Apneic pauses were noted in 67% of the severe disease group, compared with 28% of the infants who didn’t need the ICU.

The pertussis patients admitted to the pediatric ICU averaged 1 month of age, compared with age 2 months in the nonsevere group.

The maximum leukocyte, lymphocyte, and neutrophil counts during the hospital stay of the severe disease group averaged 23,600 cells/mm3, 18,000/mm3, and 5,000/mm3, respectively, significantly greater than the 15,300, 10,700, and 3,900 cells/mm3 in infants who did not require the ICU. Levels of all three cells also were higher at admission in the severe pertussis group than in those who didn’t make it to the ICU, albeit not statistically significantly so.

Dr. Arranz reported having no financial conflicts of interest regarding her study.
 
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Key clinical point: The presence of apnea in an infant admitted for pertussis is an early indicator of severe disease.

Major finding: Among infants hospitalized for pertussis, apneic pauses were present in two-thirds of those with severe disease, ultimately resulting in admission to the pediatric ICU, compared with 28% of those who didn’t require an ICU stay.

Data source: This retrospective observational study sought to identify factors associated with severe pertussis requiring an ICU stay in a group of 101 Spanish infants hospitalized with the disease.

Disclosures: The presenter reported having no financial conflicts of interest regarding her study.

MMR vaccine cut hospitalizations for unrelated respiratory infections

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The MMR vaccine appears to reduce pediatric hospitalizations not only for measles and mumps, but also for unrelated respiratory infections, said Giuseppe La Torre of the Sapienza University of Rome and his associates.

The 2-year retrospective database study included 11,004 children, 21% of whom did not receive the MMR vaccine; 49% received one dose, and 30% received two doses. There were 12 hospitalizations for measles (9 in unvaccinated children, 3 in those who received one dose, and none in those who received two doses), 2 hospitalizations for mumps (1 among vaccinated and 1 among unvaccinated children), and no hospitalizations for rubella (P less than .001).

copyright luiscar/Thinkstock
MMR vaccine was highly protective against measles hospitalizations (hazard ratio, 0.09) or measles and mumps hospitalizations (hazard ratio, 0.10).

There were 414 hospitalizations for all infectious diseases, 11% in unvaccinated children, 1.5% in those who had received one dose of vaccine, and 1% in those who had received two doses (P less than .001). MMR vaccine also was highly protective against hospitalizations for all infectious diseases (HR, 0.29).

Of 809 hospitalizations for respiratory diseases, 18% involved children who had not been vaccinated, 4% involved children who had received one dose, and 5.5% involved children vaccinated with two doses (P less than .001). MMR likewise was highly protective against hospitalizations for respiratory diseases (HR, 0.18).

Read more in the journal Human Vaccines & Immunotherapeutics (2017 Jun 12. doi: 10.1080/21645515.2017.1330733).

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The MMR vaccine appears to reduce pediatric hospitalizations not only for measles and mumps, but also for unrelated respiratory infections, said Giuseppe La Torre of the Sapienza University of Rome and his associates.

The 2-year retrospective database study included 11,004 children, 21% of whom did not receive the MMR vaccine; 49% received one dose, and 30% received two doses. There were 12 hospitalizations for measles (9 in unvaccinated children, 3 in those who received one dose, and none in those who received two doses), 2 hospitalizations for mumps (1 among vaccinated and 1 among unvaccinated children), and no hospitalizations for rubella (P less than .001).

copyright luiscar/Thinkstock
MMR vaccine was highly protective against measles hospitalizations (hazard ratio, 0.09) or measles and mumps hospitalizations (hazard ratio, 0.10).

There were 414 hospitalizations for all infectious diseases, 11% in unvaccinated children, 1.5% in those who had received one dose of vaccine, and 1% in those who had received two doses (P less than .001). MMR vaccine also was highly protective against hospitalizations for all infectious diseases (HR, 0.29).

Of 809 hospitalizations for respiratory diseases, 18% involved children who had not been vaccinated, 4% involved children who had received one dose, and 5.5% involved children vaccinated with two doses (P less than .001). MMR likewise was highly protective against hospitalizations for respiratory diseases (HR, 0.18).

Read more in the journal Human Vaccines & Immunotherapeutics (2017 Jun 12. doi: 10.1080/21645515.2017.1330733).

 

The MMR vaccine appears to reduce pediatric hospitalizations not only for measles and mumps, but also for unrelated respiratory infections, said Giuseppe La Torre of the Sapienza University of Rome and his associates.

The 2-year retrospective database study included 11,004 children, 21% of whom did not receive the MMR vaccine; 49% received one dose, and 30% received two doses. There were 12 hospitalizations for measles (9 in unvaccinated children, 3 in those who received one dose, and none in those who received two doses), 2 hospitalizations for mumps (1 among vaccinated and 1 among unvaccinated children), and no hospitalizations for rubella (P less than .001).

copyright luiscar/Thinkstock
MMR vaccine was highly protective against measles hospitalizations (hazard ratio, 0.09) or measles and mumps hospitalizations (hazard ratio, 0.10).

There were 414 hospitalizations for all infectious diseases, 11% in unvaccinated children, 1.5% in those who had received one dose of vaccine, and 1% in those who had received two doses (P less than .001). MMR vaccine also was highly protective against hospitalizations for all infectious diseases (HR, 0.29).

Of 809 hospitalizations for respiratory diseases, 18% involved children who had not been vaccinated, 4% involved children who had received one dose, and 5.5% involved children vaccinated with two doses (P less than .001). MMR likewise was highly protective against hospitalizations for respiratory diseases (HR, 0.18).

Read more in the journal Human Vaccines & Immunotherapeutics (2017 Jun 12. doi: 10.1080/21645515.2017.1330733).

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FROM HUMAN VACCINES & IMMUNOTHERAPEUTICS

Disallow All Ads
Content Gating
No Gating (article Unlocked/Free)
Alternative CME