Pulmonary Health Hub

WASHINGTON – Reactivation of tuberculosis and hepatitis B infections after starting treatment with anti–tumor necrosis factor therapy was “rare” in a large national cohort study of veterans with inflammatory bowel disease, Dr. Jason Hou reported at the annual Digestive Disease Week.

The estimated rate of tuberculosis reactivations was 2.8 per 10,000 patient-years of exposure to anti-TNF therapy “in a fairly well-screened cohort of IBD patients,” said Dr. Hou, codirector of the Inflammatory Bowel Disease Center at Baylor College of Medicine, Houston. The estimate for HBV reactivation or acute liver failure in this cohort was less than 1.4 per 10,000 patient-years of exposure, he noted.

CDC/Dr. Erskine Palmer

Practice guidelines recommend that patients with IBD should be screened for latent tuberculosis and HBV before starting treatment with an anti-TNF drug, but how often reactivation actually occurs in this population is not known, he pointed out. Moreover, recent studies have questioned the cost-effectiveness of universal screening for HBV before starting treatment, and TB reactivation rates in patients with IBD treated with anti-TNF drugs “have not been assessed on a national population level.”

Dr. Hou and his associates used a national Veterans Affairs database to identify patients who had been diagnosed between 2003 and 2011 with Crohn’s disease or ulcerative colitis, based on ICD-9 codes, and had filled at least one prescription for infliximab, adalimumab, or certolizumab pegol; they also looked for codes related to possible tuberculosis reactivation or acute liver failure related to HBV reactivation at the time of or after anti-TNF therapy was started. Cases were then verified by reviewing electronic medical records of patients to confirm the diagnosis of tuberculosis or HBV, exposure to an anti-TNF drug, and completion of pretreatment screening.

They identified 3,357 patients with IBD who had received a prescription for an anti-TNF treatment, representing 7,210 patient-years of anti-TNF treatment; most were men and were white. The mean time on treatment was about 2 years, and they had started treatment at a mean age of 57 years. Screening rates for tuberculosis were relatively high and remained stable throughout the study period, at 72% overall, but HBV screening rates were low, at 24% overall. HBV screening was not included in practice guidelines until 2006, and the rate significantly increased from under 10% at the beginning of the period studied to 42% at the end, Dr. Hou noted.

They identified 23 patients with ICD-9 codes related to tuberculosis occurring after they started anti-TNF therapy, but “on chart review, only two patients were confirmed to have tuberculosis reactivation” related to anti-TNF therapy, which occurred at 8 and 18 months of treatment, he said. “Very interestingly, both of these patients had latent tuberculosis and documented completed courses of INH [isonicotinylhydrazine] and a negative chest x-ray prior to [anti-]TNF initiation.” Because the only cases of tuberculosis reactivation occurred in patients with a prior history of latent tuberculosis, “we should maintain extra diligence in those patients even if appropriate screening has been performed,” he advised.

They identified 12 patients with codes related to hepatitis B after the treatment started, two had clinically relevant outcomes, but the chart review indicated that neither case was HPV reactivation. There were two cases of patients with positive HBV tests. One of these patients, who developed acute jaundice with serologies consistent with acute HBV infection, reported a possible exposure to HBV and was newly diagnosed with HIV, associated with the same encounter. This patient was on infliximab and continued treatment, and HBV viremia spontaneously cleared without antiviral treatment, Dr. Hou said.

The second “clinically relevant” case was a patient with chronic HBV infection, identified in a presurgical screen, who was asymptomatic and had normal liver function tests. Infliximab was discontinued and the patient started antiviral therapy; viremia resolved and the patient resumed treatment with infliximab “without complications,” Dr. Hou said.

Another four patients were identified related to codes for acute liver failure, but on chart review, none had liver failure related to hepatitis B.

The study’s limitations include the possibility that patients may receive medical care outside the VA system, which would not be picked up in the analysis, he said, but added, “when we look at our estimate of tuberculosis reactivation, they mirror almost exactly those reported in the rheumatology literature in screened populations.” Another limitation is that the study depended on the accuracy of ICD-9 codes for the diagnoses, but all outcomes were verified in the chart review, he said.

Dr. Hou is also director of Inflammatory Bowel Diseases and an investigator in the clinical epidemiology and outcomes program in the Center for Innovations in Quality Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston.

His financial disclosures include receiving consulting, speaking, teaching, and/or advisory fees from Janssen, Aptalis, and AbbVie.

[email protected]

WASHINGTON – Reactivation of tuberculosis and hepatitis B infections after starting treatment with anti–tumor necrosis factor therapy was “rare” in a large national cohort study of veterans with inflammatory bowel disease, Dr. Jason Hou reported at the annual Digestive Disease Week.

The estimated rate of tuberculosis reactivations was 2.8 per 10,000 patient-years of exposure to anti-TNF therapy “in a fairly well-screened cohort of IBD patients,” said Dr. Hou, codirector of the Inflammatory Bowel Disease Center at Baylor College of Medicine, Houston. The estimate for HBV reactivation or acute liver failure in this cohort was less than 1.4 per 10,000 patient-years of exposure, he noted.

CDC/Dr. Erskine Palmer

Practice guidelines recommend that patients with IBD should be screened for latent tuberculosis and HBV before starting treatment with an anti-TNF drug, but how often reactivation actually occurs in this population is not known, he pointed out. Moreover, recent studies have questioned the cost-effectiveness of universal screening for HBV before starting treatment, and TB reactivation rates in patients with IBD treated with anti-TNF drugs “have not been assessed on a national population level.”

Dr. Hou and his associates used a national Veterans Affairs database to identify patients who had been diagnosed between 2003 and 2011 with Crohn’s disease or ulcerative colitis, based on ICD-9 codes, and had filled at least one prescription for infliximab, adalimumab, or certolizumab pegol; they also looked for codes related to possible tuberculosis reactivation or acute liver failure related to HBV reactivation at the time of or after anti-TNF therapy was started. Cases were then verified by reviewing electronic medical records of patients to confirm the diagnosis of tuberculosis or HBV, exposure to an anti-TNF drug, and completion of pretreatment screening.

They identified 3,357 patients with IBD who had received a prescription for an anti-TNF treatment, representing 7,210 patient-years of anti-TNF treatment; most were men and were white. The mean time on treatment was about 2 years, and they had started treatment at a mean age of 57 years. Screening rates for tuberculosis were relatively high and remained stable throughout the study period, at 72% overall, but HBV screening rates were low, at 24% overall. HBV screening was not included in practice guidelines until 2006, and the rate significantly increased from under 10% at the beginning of the period studied to 42% at the end, Dr. Hou noted.

They identified 23 patients with ICD-9 codes related to tuberculosis occurring after they started anti-TNF therapy, but “on chart review, only two patients were confirmed to have tuberculosis reactivation” related to anti-TNF therapy, which occurred at 8 and 18 months of treatment, he said. “Very interestingly, both of these patients had latent tuberculosis and documented completed courses of INH [isonicotinylhydrazine] and a negative chest x-ray prior to [anti-]TNF initiation.” Because the only cases of tuberculosis reactivation occurred in patients with a prior history of latent tuberculosis, “we should maintain extra diligence in those patients even if appropriate screening has been performed,” he advised.

They identified 12 patients with codes related to hepatitis B after the treatment started, two had clinically relevant outcomes, but the chart review indicated that neither case was HPV reactivation. There were two cases of patients with positive HBV tests. One of these patients, who developed acute jaundice with serologies consistent with acute HBV infection, reported a possible exposure to HBV and was newly diagnosed with HIV, associated with the same encounter. This patient was on infliximab and continued treatment, and HBV viremia spontaneously cleared without antiviral treatment, Dr. Hou said.

The second “clinically relevant” case was a patient with chronic HBV infection, identified in a presurgical screen, who was asymptomatic and had normal liver function tests. Infliximab was discontinued and the patient started antiviral therapy; viremia resolved and the patient resumed treatment with infliximab “without complications,” Dr. Hou said.

Another four patients were identified related to codes for acute liver failure, but on chart review, none had liver failure related to hepatitis B.

The study’s limitations include the possibility that patients may receive medical care outside the VA system, which would not be picked up in the analysis, he said, but added, “when we look at our estimate of tuberculosis reactivation, they mirror almost exactly those reported in the rheumatology literature in screened populations.” Another limitation is that the study depended on the accuracy of ICD-9 codes for the diagnoses, but all outcomes were verified in the chart review, he said.

Dr. Hou is also director of Inflammatory Bowel Diseases and an investigator in the clinical epidemiology and outcomes program in the Center for Innovations in Quality Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston.

His financial disclosures include receiving consulting, speaking, teaching, and/or advisory fees from Janssen, Aptalis, and AbbVie.

[email protected]

WASHINGTON – Reactivation of tuberculosis and hepatitis B infections after starting treatment with anti–tumor necrosis factor therapy was “rare” in a large national cohort study of veterans with inflammatory bowel disease, Dr. Jason Hou reported at the annual Digestive Disease Week.

The estimated rate of tuberculosis reactivations was 2.8 per 10,000 patient-years of exposure to anti-TNF therapy “in a fairly well-screened cohort of IBD patients,” said Dr. Hou, codirector of the Inflammatory Bowel Disease Center at Baylor College of Medicine, Houston. The estimate for HBV reactivation or acute liver failure in this cohort was less than 1.4 per 10,000 patient-years of exposure, he noted.

CDC/Dr. Erskine Palmer

Practice guidelines recommend that patients with IBD should be screened for latent tuberculosis and HBV before starting treatment with an anti-TNF drug, but how often reactivation actually occurs in this population is not known, he pointed out. Moreover, recent studies have questioned the cost-effectiveness of universal screening for HBV before starting treatment, and TB reactivation rates in patients with IBD treated with anti-TNF drugs “have not been assessed on a national population level.”

Dr. Hou and his associates used a national Veterans Affairs database to identify patients who had been diagnosed between 2003 and 2011 with Crohn’s disease or ulcerative colitis, based on ICD-9 codes, and had filled at least one prescription for infliximab, adalimumab, or certolizumab pegol; they also looked for codes related to possible tuberculosis reactivation or acute liver failure related to HBV reactivation at the time of or after anti-TNF therapy was started. Cases were then verified by reviewing electronic medical records of patients to confirm the diagnosis of tuberculosis or HBV, exposure to an anti-TNF drug, and completion of pretreatment screening.

They identified 3,357 patients with IBD who had received a prescription for an anti-TNF treatment, representing 7,210 patient-years of anti-TNF treatment; most were men and were white. The mean time on treatment was about 2 years, and they had started treatment at a mean age of 57 years. Screening rates for tuberculosis were relatively high and remained stable throughout the study period, at 72% overall, but HBV screening rates were low, at 24% overall. HBV screening was not included in practice guidelines until 2006, and the rate significantly increased from under 10% at the beginning of the period studied to 42% at the end, Dr. Hou noted.

They identified 23 patients with ICD-9 codes related to tuberculosis occurring after they started anti-TNF therapy, but “on chart review, only two patients were confirmed to have tuberculosis reactivation” related to anti-TNF therapy, which occurred at 8 and 18 months of treatment, he said. “Very interestingly, both of these patients had latent tuberculosis and documented completed courses of INH [isonicotinylhydrazine] and a negative chest x-ray prior to [anti-]TNF initiation.” Because the only cases of tuberculosis reactivation occurred in patients with a prior history of latent tuberculosis, “we should maintain extra diligence in those patients even if appropriate screening has been performed,” he advised.

They identified 12 patients with codes related to hepatitis B after the treatment started, two had clinically relevant outcomes, but the chart review indicated that neither case was HPV reactivation. There were two cases of patients with positive HBV tests. One of these patients, who developed acute jaundice with serologies consistent with acute HBV infection, reported a possible exposure to HBV and was newly diagnosed with HIV, associated with the same encounter. This patient was on infliximab and continued treatment, and HBV viremia spontaneously cleared without antiviral treatment, Dr. Hou said.

The second “clinically relevant” case was a patient with chronic HBV infection, identified in a presurgical screen, who was asymptomatic and had normal liver function tests. Infliximab was discontinued and the patient started antiviral therapy; viremia resolved and the patient resumed treatment with infliximab “without complications,” Dr. Hou said.

Another four patients were identified related to codes for acute liver failure, but on chart review, none had liver failure related to hepatitis B.

The study’s limitations include the possibility that patients may receive medical care outside the VA system, which would not be picked up in the analysis, he said, but added, “when we look at our estimate of tuberculosis reactivation, they mirror almost exactly those reported in the rheumatology literature in screened populations.” Another limitation is that the study depended on the accuracy of ICD-9 codes for the diagnoses, but all outcomes were verified in the chart review, he said.

Dr. Hou is also director of Inflammatory Bowel Diseases and an investigator in the clinical epidemiology and outcomes program in the Center for Innovations in Quality Effectiveness and Safety at the Michael E. DeBakey VA Medical Center, Houston.

His financial disclosures include receiving consulting, speaking, teaching, and/or advisory fees from Janssen, Aptalis, and AbbVie.

[email protected]

DENVER – Intermittent high-dose nitric oxide (NO) inhalation therapy appears safe and shows clear signals of efficacy in infants hospitalized with bronchiolitis, a randomized controlled trial showed.

“Further larger scale clinical trials are needed to establish its role in lower respiratory tract infections such as viral bronchiolitis, pneumonia, cystic fibrosis, viral-related asthma, COPD [chronic obstructive pulmonary disease], and more,” one of the study authors, Yossef Av-Gay, Ph.D., said in an interview in advance of an international conference of the American Thoracic Society.

In what they said is the first human study of its kind, researchers led by Dr. Asher Tal, head of the pediatric pulmonary unit at Soroka University Medical Center, Beer Sheva, Israel, set out to determine the safety and tolerability of intermittent high-dose inhaled NO for the treatment of hospitalized infants aged 2-12 months with bronchiolitis. Patients received either 160 parts per million (ppm) of NO five times per day for 30 minutes each time or oxygen only.

At lower concentrations, nitric oxide is a pulmonary vasodilator. It has been studied in the 1-60 ppm range and received Food and Drug Administration approval in 1999.* "Nitric oxide gas is used to treat neonates at lower dose, and in this study we investigated its antimicrobial dosage, which is higher than current treatment,” said Dr. Av-Gay, professor of the division of infectious diseases at the University of British Columbia, Vancouver.

“Previous in-vitro and in animal studies support the antimicrobial effect of intermittent inhalations of 160 ppm of NO to treat lower respiratory tract infections, both viral and bacterial. Bronchiolitis is a viral-related [infection] that causes significant morbidity and even mortality in infants around the world. Presently the treatment protocol for hospitalized infants is supportive care only, because despite many years of research as there is not yet an available treatment or specific anti-viral drug. Inhaled NO is thus an exciting potential novel drug for the treatment of acute bronchiolitis,” he said.

Of 43 infants initially enrolled, 25 were hospitalized for more than 24 hours and were considered evaluable for efficacy. Of these, 14 received intermittent high-dose inhaled NO and 11 received oxygen only. The researchers observed no significant differences between the NO and oxygen groups in the number of adverse events or in the number of serious adverse events. Patients who received NO, however, spent significantly fewer hours in the hospital, compared with the oxygen group (mean of 46 hours vs. 74 hours, respectively; P = .032) and reached 92% oxygen saturation in significantly faster time (mean of 26 hours vs. 61 hours; P = .032).

Dr. Av-Gay acknowledged certain limitations of the analysis, including the fact that the study’s primary outcome was safety and tolerability. “Therefore, the study was not powered to show efficacy,” he said.

The study was funded by Advanced Inhalation Therapies, an Israeli-based company that holds the rights to the NO technology. Dr. Av-Gay is the company’s chief scientific officer, and Dr. Tal is employed by the company.

[email protected]

On Twitter @dougbrunk

*This article was added to on 6/25/15.

DENVER – Intermittent high-dose nitric oxide (NO) inhalation therapy appears safe and shows clear signals of efficacy in infants hospitalized with bronchiolitis, a randomized controlled trial showed.

“Further larger scale clinical trials are needed to establish its role in lower respiratory tract infections such as viral bronchiolitis, pneumonia, cystic fibrosis, viral-related asthma, COPD [chronic obstructive pulmonary disease], and more,” one of the study authors, Yossef Av-Gay, Ph.D., said in an interview in advance of an international conference of the American Thoracic Society.

In what they said is the first human study of its kind, researchers led by Dr. Asher Tal, head of the pediatric pulmonary unit at Soroka University Medical Center, Beer Sheva, Israel, set out to determine the safety and tolerability of intermittent high-dose inhaled NO for the treatment of hospitalized infants aged 2-12 months with bronchiolitis. Patients received either 160 parts per million (ppm) of NO five times per day for 30 minutes each time or oxygen only.

At lower concentrations, nitric oxide is a pulmonary vasodilator. It has been studied in the 1-60 ppm range and received Food and Drug Administration approval in 1999.* "Nitric oxide gas is used to treat neonates at lower dose, and in this study we investigated its antimicrobial dosage, which is higher than current treatment,” said Dr. Av-Gay, professor of the division of infectious diseases at the University of British Columbia, Vancouver.

“Previous in-vitro and in animal studies support the antimicrobial effect of intermittent inhalations of 160 ppm of NO to treat lower respiratory tract infections, both viral and bacterial. Bronchiolitis is a viral-related [infection] that causes significant morbidity and even mortality in infants around the world. Presently the treatment protocol for hospitalized infants is supportive care only, because despite many years of research as there is not yet an available treatment or specific anti-viral drug. Inhaled NO is thus an exciting potential novel drug for the treatment of acute bronchiolitis,” he said.

Of 43 infants initially enrolled, 25 were hospitalized for more than 24 hours and were considered evaluable for efficacy. Of these, 14 received intermittent high-dose inhaled NO and 11 received oxygen only. The researchers observed no significant differences between the NO and oxygen groups in the number of adverse events or in the number of serious adverse events. Patients who received NO, however, spent significantly fewer hours in the hospital, compared with the oxygen group (mean of 46 hours vs. 74 hours, respectively; P = .032) and reached 92% oxygen saturation in significantly faster time (mean of 26 hours vs. 61 hours; P = .032).

Dr. Av-Gay acknowledged certain limitations of the analysis, including the fact that the study’s primary outcome was safety and tolerability. “Therefore, the study was not powered to show efficacy,” he said.

The study was funded by Advanced Inhalation Therapies, an Israeli-based company that holds the rights to the NO technology. Dr. Av-Gay is the company’s chief scientific officer, and Dr. Tal is employed by the company.

[email protected]

On Twitter @dougbrunk

*This article was added to on 6/25/15.

DENVER – Intermittent high-dose nitric oxide (NO) inhalation therapy appears safe and shows clear signals of efficacy in infants hospitalized with bronchiolitis, a randomized controlled trial showed.

“Further larger scale clinical trials are needed to establish its role in lower respiratory tract infections such as viral bronchiolitis, pneumonia, cystic fibrosis, viral-related asthma, COPD [chronic obstructive pulmonary disease], and more,” one of the study authors, Yossef Av-Gay, Ph.D., said in an interview in advance of an international conference of the American Thoracic Society.

In what they said is the first human study of its kind, researchers led by Dr. Asher Tal, head of the pediatric pulmonary unit at Soroka University Medical Center, Beer Sheva, Israel, set out to determine the safety and tolerability of intermittent high-dose inhaled NO for the treatment of hospitalized infants aged 2-12 months with bronchiolitis. Patients received either 160 parts per million (ppm) of NO five times per day for 30 minutes each time or oxygen only.

At lower concentrations, nitric oxide is a pulmonary vasodilator. It has been studied in the 1-60 ppm range and received Food and Drug Administration approval in 1999.* "Nitric oxide gas is used to treat neonates at lower dose, and in this study we investigated its antimicrobial dosage, which is higher than current treatment,” said Dr. Av-Gay, professor of the division of infectious diseases at the University of British Columbia, Vancouver.

“Previous in-vitro and in animal studies support the antimicrobial effect of intermittent inhalations of 160 ppm of NO to treat lower respiratory tract infections, both viral and bacterial. Bronchiolitis is a viral-related [infection] that causes significant morbidity and even mortality in infants around the world. Presently the treatment protocol for hospitalized infants is supportive care only, because despite many years of research as there is not yet an available treatment or specific anti-viral drug. Inhaled NO is thus an exciting potential novel drug for the treatment of acute bronchiolitis,” he said.

Of 43 infants initially enrolled, 25 were hospitalized for more than 24 hours and were considered evaluable for efficacy. Of these, 14 received intermittent high-dose inhaled NO and 11 received oxygen only. The researchers observed no significant differences between the NO and oxygen groups in the number of adverse events or in the number of serious adverse events. Patients who received NO, however, spent significantly fewer hours in the hospital, compared with the oxygen group (mean of 46 hours vs. 74 hours, respectively; P = .032) and reached 92% oxygen saturation in significantly faster time (mean of 26 hours vs. 61 hours; P = .032).

Dr. Av-Gay acknowledged certain limitations of the analysis, including the fact that the study’s primary outcome was safety and tolerability. “Therefore, the study was not powered to show efficacy,” he said.

The study was funded by Advanced Inhalation Therapies, an Israeli-based company that holds the rights to the NO technology. Dr. Av-Gay is the company’s chief scientific officer, and Dr. Tal is employed by the company.

[email protected]

On Twitter @dougbrunk

*This article was added to on 6/25/15.

DENVER – The use of nintedanib 150 mg twice daily has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis up to 76 weeks of treatment, with an acceptable safety and tolerability profile, according to results from a novel study.

Marketed by Boehringer Ingelheim, nintedanib (Ofev)was approved by the FDA in October of 2014 for the treatment of idiopathic pulmonary fibrosis. Data from period 1 of the dose-finding, phase II TOMORROW trial (N. Engl. J. Med. 2011;365:1079–87) and the two replicate Phase III INPULSIS trials (N. Engl. J. Med. 2014;370:2071-82) demonstrated the efficacy and safety of nintedanib 150 mg twice daily over 52 weeks in patients with IPF. After completing period 1 of the TOMORROW trial, study participants had the option to continue treatment in a further blinded treatment phase (period 2).

“Clinicians are always interested in the long-term efficacy and safety of a new drug in patients suffering from a chronic, progressive disease like IPF,” lead study author Dr. Luca Richeldi said in an interview in advance of an international conference of the American Thoracic Society. “These data from period 2 of the TOMORROW trial are the first data to be generated on long-term treatment with nintedanib, i.e., beyond 52 weeks.” In period 2, patients treated with nintedanib in period 1 continued their dose, while placebo-treated patients were switched to nintedanib 50 mg once daily. The researchers evaluated change in forced vital capacity (FVC), acute exacerbations, mortality and adverse events in the nintedanib 150 mg twice daily group vs. the comparator group (placebo/nintedanib 50 mg once daily).

Of the 428 patients treated in period 1, 316 patients completed period 1 and 286 patients continued treatment in period 2. Of these 286 patients, 48 continued to receive nintedanib 150 mg twice daily and 54 were switched from placebo to nintedanib 50 mg once daily (comparator group), said Dr. Richeldi, professor of respiratory medicine and chair of interstitial lung disease at the University of Southampton (United Kingdom).

Dr. Richeldi reported results from a mean exposure of 14.2 months for the nintedanib 150 mg twice daily group and 16.8 months for the comparator group. Across periods 1 and 2, the researchers observed that the mean change in forced vital capacity (FVC) was consistently lower in the nintedanib 150 mg twice daily group, compared with the comparator group, such that by week 76 the absolute change in the percentage of predicted FVC was -3.1% vs. -6.3%, respectively. In addition, the incidence of acute exacerbations at week 76 was lower in the nintedanib 150 mg twice daily group, compared with the comparator group (3.2 vs. 13.4 per 100 patient-years).

A total of 14 patients (16.3%) died in the nintedanib 150 mg twice daily group, compared with 19 patients (21.8%) in the comparator group. However, the proportion of patients with at least one adverse event across period 1 and 2 was similar between both groups (97.6% vs. 96.5%, respectively), as was the proportion of patients with at least one serious adverse event (30.6% vs. 35.3%).

“It was not a surprise to see that the effect of nintedanib 150 mg twice daily on slowing disease progression (as shown by a reduced decline in FVC) was maintained up to week 76,” Dr. Richeldi said. “In addition, we expected that no relevant changes in the safety and tolerability of nintedanib would be observed in period 2 compared with period 1. We were impressed to see that over 90% of patients who completed the first 52 weeks of treatment in the TOMORROW trial (period 1) chose to continue to receive treatment in period 2.”

One limitation of the study was its small sample size, he said, “with FVC data only being available for 80 patients treated with nintedanib twice daily or comparator at week 76. Data from the open-label extension of the INPULSIS trials, INPULSIS-ON, will provide additional data on the long-term efficacy and safety of nintedanib 150 mg twice daily in patients with IPF.”

The study was supported by Boehringer Ingelheim. Dr. Richeldi disclosed that he has received consultation and speaker’s fees from the company. He was also a member of the steering committee for the TOMORROW trial.

[email protected]

On Twitter @dougbrunk

DENVER – The use of nintedanib 150 mg twice daily has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis up to 76 weeks of treatment, with an acceptable safety and tolerability profile, according to results from a novel study.

Marketed by Boehringer Ingelheim, nintedanib (Ofev)was approved by the FDA in October of 2014 for the treatment of idiopathic pulmonary fibrosis. Data from period 1 of the dose-finding, phase II TOMORROW trial (N. Engl. J. Med. 2011;365:1079–87) and the two replicate Phase III INPULSIS trials (N. Engl. J. Med. 2014;370:2071-82) demonstrated the efficacy and safety of nintedanib 150 mg twice daily over 52 weeks in patients with IPF. After completing period 1 of the TOMORROW trial, study participants had the option to continue treatment in a further blinded treatment phase (period 2).

“Clinicians are always interested in the long-term efficacy and safety of a new drug in patients suffering from a chronic, progressive disease like IPF,” lead study author Dr. Luca Richeldi said in an interview in advance of an international conference of the American Thoracic Society. “These data from period 2 of the TOMORROW trial are the first data to be generated on long-term treatment with nintedanib, i.e., beyond 52 weeks.” In period 2, patients treated with nintedanib in period 1 continued their dose, while placebo-treated patients were switched to nintedanib 50 mg once daily. The researchers evaluated change in forced vital capacity (FVC), acute exacerbations, mortality and adverse events in the nintedanib 150 mg twice daily group vs. the comparator group (placebo/nintedanib 50 mg once daily).

Of the 428 patients treated in period 1, 316 patients completed period 1 and 286 patients continued treatment in period 2. Of these 286 patients, 48 continued to receive nintedanib 150 mg twice daily and 54 were switched from placebo to nintedanib 50 mg once daily (comparator group), said Dr. Richeldi, professor of respiratory medicine and chair of interstitial lung disease at the University of Southampton (United Kingdom).

Dr. Richeldi reported results from a mean exposure of 14.2 months for the nintedanib 150 mg twice daily group and 16.8 months for the comparator group. Across periods 1 and 2, the researchers observed that the mean change in forced vital capacity (FVC) was consistently lower in the nintedanib 150 mg twice daily group, compared with the comparator group, such that by week 76 the absolute change in the percentage of predicted FVC was -3.1% vs. -6.3%, respectively. In addition, the incidence of acute exacerbations at week 76 was lower in the nintedanib 150 mg twice daily group, compared with the comparator group (3.2 vs. 13.4 per 100 patient-years).

A total of 14 patients (16.3%) died in the nintedanib 150 mg twice daily group, compared with 19 patients (21.8%) in the comparator group. However, the proportion of patients with at least one adverse event across period 1 and 2 was similar between both groups (97.6% vs. 96.5%, respectively), as was the proportion of patients with at least one serious adverse event (30.6% vs. 35.3%).

“It was not a surprise to see that the effect of nintedanib 150 mg twice daily on slowing disease progression (as shown by a reduced decline in FVC) was maintained up to week 76,” Dr. Richeldi said. “In addition, we expected that no relevant changes in the safety and tolerability of nintedanib would be observed in period 2 compared with period 1. We were impressed to see that over 90% of patients who completed the first 52 weeks of treatment in the TOMORROW trial (period 1) chose to continue to receive treatment in period 2.”

One limitation of the study was its small sample size, he said, “with FVC data only being available for 80 patients treated with nintedanib twice daily or comparator at week 76. Data from the open-label extension of the INPULSIS trials, INPULSIS-ON, will provide additional data on the long-term efficacy and safety of nintedanib 150 mg twice daily in patients with IPF.”

The study was supported by Boehringer Ingelheim. Dr. Richeldi disclosed that he has received consultation and speaker’s fees from the company. He was also a member of the steering committee for the TOMORROW trial.

[email protected]

On Twitter @dougbrunk

DENVER – The use of nintedanib 150 mg twice daily has been shown to slow disease progression in patients with idiopathic pulmonary fibrosis up to 76 weeks of treatment, with an acceptable safety and tolerability profile, according to results from a novel study.

Marketed by Boehringer Ingelheim, nintedanib (Ofev)was approved by the FDA in October of 2014 for the treatment of idiopathic pulmonary fibrosis. Data from period 1 of the dose-finding, phase II TOMORROW trial (N. Engl. J. Med. 2011;365:1079–87) and the two replicate Phase III INPULSIS trials (N. Engl. J. Med. 2014;370:2071-82) demonstrated the efficacy and safety of nintedanib 150 mg twice daily over 52 weeks in patients with IPF. After completing period 1 of the TOMORROW trial, study participants had the option to continue treatment in a further blinded treatment phase (period 2).

“Clinicians are always interested in the long-term efficacy and safety of a new drug in patients suffering from a chronic, progressive disease like IPF,” lead study author Dr. Luca Richeldi said in an interview in advance of an international conference of the American Thoracic Society. “These data from period 2 of the TOMORROW trial are the first data to be generated on long-term treatment with nintedanib, i.e., beyond 52 weeks.” In period 2, patients treated with nintedanib in period 1 continued their dose, while placebo-treated patients were switched to nintedanib 50 mg once daily. The researchers evaluated change in forced vital capacity (FVC), acute exacerbations, mortality and adverse events in the nintedanib 150 mg twice daily group vs. the comparator group (placebo/nintedanib 50 mg once daily).

Of the 428 patients treated in period 1, 316 patients completed period 1 and 286 patients continued treatment in period 2. Of these 286 patients, 48 continued to receive nintedanib 150 mg twice daily and 54 were switched from placebo to nintedanib 50 mg once daily (comparator group), said Dr. Richeldi, professor of respiratory medicine and chair of interstitial lung disease at the University of Southampton (United Kingdom).

Dr. Richeldi reported results from a mean exposure of 14.2 months for the nintedanib 150 mg twice daily group and 16.8 months for the comparator group. Across periods 1 and 2, the researchers observed that the mean change in forced vital capacity (FVC) was consistently lower in the nintedanib 150 mg twice daily group, compared with the comparator group, such that by week 76 the absolute change in the percentage of predicted FVC was -3.1% vs. -6.3%, respectively. In addition, the incidence of acute exacerbations at week 76 was lower in the nintedanib 150 mg twice daily group, compared with the comparator group (3.2 vs. 13.4 per 100 patient-years).

A total of 14 patients (16.3%) died in the nintedanib 150 mg twice daily group, compared with 19 patients (21.8%) in the comparator group. However, the proportion of patients with at least one adverse event across period 1 and 2 was similar between both groups (97.6% vs. 96.5%, respectively), as was the proportion of patients with at least one serious adverse event (30.6% vs. 35.3%).

“It was not a surprise to see that the effect of nintedanib 150 mg twice daily on slowing disease progression (as shown by a reduced decline in FVC) was maintained up to week 76,” Dr. Richeldi said. “In addition, we expected that no relevant changes in the safety and tolerability of nintedanib would be observed in period 2 compared with period 1. We were impressed to see that over 90% of patients who completed the first 52 weeks of treatment in the TOMORROW trial (period 1) chose to continue to receive treatment in period 2.”

One limitation of the study was its small sample size, he said, “with FVC data only being available for 80 patients treated with nintedanib twice daily or comparator at week 76. Data from the open-label extension of the INPULSIS trials, INPULSIS-ON, will provide additional data on the long-term efficacy and safety of nintedanib 150 mg twice daily in patients with IPF.”

The study was supported by Boehringer Ingelheim. Dr. Richeldi disclosed that he has received consultation and speaker’s fees from the company. He was also a member of the steering committee for the TOMORROW trial.

[email protected]

On Twitter @dougbrunk

SEATTLE – Smoking is related to prevalent and incident joint pain in patients who have knee osteoarthritis or are at high risk for it, but the mechanism of this association is unclear, in a study of 3,026 patients.

“Previous studies have shown that compared to nonsmokers, smokers have more musculoskeletal pain and report more severe pain,” Jingbo Niu, D.Sc. of the Clinical Epidemiology Research & Training Unit at Boston University reported at the World Congress on Osteoarthritis.

Possible mechanisms include down-regulation of the hypothalamic-pituitary-adrenal axis or triggering of nicotine-sensitive acetylcholine receptors in the dorsal root ganglion. “These factors may translate to a change in pain perception among smokers,” she said.

Dr. Niu and her colleagues analyzed data from the Multicenter Osteoarthritis Study (MOST), a prospective cohort study of risk factors for the development and progression of knee osteoarthritis and knee pain in patients initially aged 50-79 years. They performed cross-sectional analyses at baseline and at the 7-year follow-up visit, and longitudinal analyses for the interim period.

At baseline, 56% of the cohort were never-smokers, 38% were former smokers, and 6% were current smokers, reported Dr. Niu, who disclosed that she had no relevant conflicts of interest. Smoking intensity averaged 22 pack-years.

Study results showed that at baseline, current smokers had significantly more severe knee pain than did never-smokers, with an adjusted difference of 0.83 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain scale.

Also at baseline, former smokers were more likely than were never-smokers to have widespread joint pain, defined as pain in all five regions of a joint pain homunculus (adjusted odds ratio, 1.3). And there was a dose-response relationship, whereby the greater the number of pack-years at baseline, the higher the risk of developing widespread joint pain during follow-up (P = .02).

However, neither smoking status nor smoking intensity was significantly associated with pain sensitization, assessed from the pressure pain threshold at the right wrist, according to the data reported at the meeting, which was sponsored by the Osteoarthritis Research Society International.

“We found smoking was related to knee pain severity and widespread pain, but not with pain sensitization,” Dr. Niu concluded.

“The number of current smokers in our analysis was limited,” she said. In addition, “subjects with knee pain were more likely to be recruited into the MOST study because they have a high risk of developing knee osteoarthritis. This inclusion criterion may lead to selection bias when we study knee pain and other pain-related outcomes.”

One session attendee noted that the confounders in the analyses did not include socioeconomic factors and recommended they be added. “Of course, smoking status could be confounded by socioeconomic factors, and couldn’t it just be that smoking is a surrogate measure?” he asked.

“It’s a good suggestion,” Dr. Niu agreed, noting that the data set has some socioeconomic measures, such as education, that could be incorporated into analyses.

In an interview, Dr. Timothy McAlindon, one of the session’s comoderators and a professor of medicine at Tufts University, Boston, said, “I think this is a very nicely done study looking at the association of smoking with pain in osteoarthritis.

“What they found is there is clearly a significant association of smoking with pain and incident widespread pain. What was less clear was the mechanistic relationship. Maybe they didn’t test the right mechanistic measures,” he proposed.

“If there is a causal relationship, it could perhaps suggest intervention. But I think that is very conjectural based on what they have done so far,” Dr. McAlindon concluded.

SEATTLE – Smoking is related to prevalent and incident joint pain in patients who have knee osteoarthritis or are at high risk for it, but the mechanism of this association is unclear, in a study of 3,026 patients.

“Previous studies have shown that compared to nonsmokers, smokers have more musculoskeletal pain and report more severe pain,” Jingbo Niu, D.Sc. of the Clinical Epidemiology Research & Training Unit at Boston University reported at the World Congress on Osteoarthritis.

Possible mechanisms include down-regulation of the hypothalamic-pituitary-adrenal axis or triggering of nicotine-sensitive acetylcholine receptors in the dorsal root ganglion. “These factors may translate to a change in pain perception among smokers,” she said.

Dr. Niu and her colleagues analyzed data from the Multicenter Osteoarthritis Study (MOST), a prospective cohort study of risk factors for the development and progression of knee osteoarthritis and knee pain in patients initially aged 50-79 years. They performed cross-sectional analyses at baseline and at the 7-year follow-up visit, and longitudinal analyses for the interim period.

At baseline, 56% of the cohort were never-smokers, 38% were former smokers, and 6% were current smokers, reported Dr. Niu, who disclosed that she had no relevant conflicts of interest. Smoking intensity averaged 22 pack-years.

Study results showed that at baseline, current smokers had significantly more severe knee pain than did never-smokers, with an adjusted difference of 0.83 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain scale.

Also at baseline, former smokers were more likely than were never-smokers to have widespread joint pain, defined as pain in all five regions of a joint pain homunculus (adjusted odds ratio, 1.3). And there was a dose-response relationship, whereby the greater the number of pack-years at baseline, the higher the risk of developing widespread joint pain during follow-up (P = .02).

However, neither smoking status nor smoking intensity was significantly associated with pain sensitization, assessed from the pressure pain threshold at the right wrist, according to the data reported at the meeting, which was sponsored by the Osteoarthritis Research Society International.

“We found smoking was related to knee pain severity and widespread pain, but not with pain sensitization,” Dr. Niu concluded.

“The number of current smokers in our analysis was limited,” she said. In addition, “subjects with knee pain were more likely to be recruited into the MOST study because they have a high risk of developing knee osteoarthritis. This inclusion criterion may lead to selection bias when we study knee pain and other pain-related outcomes.”

One session attendee noted that the confounders in the analyses did not include socioeconomic factors and recommended they be added. “Of course, smoking status could be confounded by socioeconomic factors, and couldn’t it just be that smoking is a surrogate measure?” he asked.

“It’s a good suggestion,” Dr. Niu agreed, noting that the data set has some socioeconomic measures, such as education, that could be incorporated into analyses.

In an interview, Dr. Timothy McAlindon, one of the session’s comoderators and a professor of medicine at Tufts University, Boston, said, “I think this is a very nicely done study looking at the association of smoking with pain in osteoarthritis.

“What they found is there is clearly a significant association of smoking with pain and incident widespread pain. What was less clear was the mechanistic relationship. Maybe they didn’t test the right mechanistic measures,” he proposed.

“If there is a causal relationship, it could perhaps suggest intervention. But I think that is very conjectural based on what they have done so far,” Dr. McAlindon concluded.

SEATTLE – Smoking is related to prevalent and incident joint pain in patients who have knee osteoarthritis or are at high risk for it, but the mechanism of this association is unclear, in a study of 3,026 patients.

“Previous studies have shown that compared to nonsmokers, smokers have more musculoskeletal pain and report more severe pain,” Jingbo Niu, D.Sc. of the Clinical Epidemiology Research & Training Unit at Boston University reported at the World Congress on Osteoarthritis.

Possible mechanisms include down-regulation of the hypothalamic-pituitary-adrenal axis or triggering of nicotine-sensitive acetylcholine receptors in the dorsal root ganglion. “These factors may translate to a change in pain perception among smokers,” she said.

Dr. Niu and her colleagues analyzed data from the Multicenter Osteoarthritis Study (MOST), a prospective cohort study of risk factors for the development and progression of knee osteoarthritis and knee pain in patients initially aged 50-79 years. They performed cross-sectional analyses at baseline and at the 7-year follow-up visit, and longitudinal analyses for the interim period.

At baseline, 56% of the cohort were never-smokers, 38% were former smokers, and 6% were current smokers, reported Dr. Niu, who disclosed that she had no relevant conflicts of interest. Smoking intensity averaged 22 pack-years.

Study results showed that at baseline, current smokers had significantly more severe knee pain than did never-smokers, with an adjusted difference of 0.83 points on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain scale.

Also at baseline, former smokers were more likely than were never-smokers to have widespread joint pain, defined as pain in all five regions of a joint pain homunculus (adjusted odds ratio, 1.3). And there was a dose-response relationship, whereby the greater the number of pack-years at baseline, the higher the risk of developing widespread joint pain during follow-up (P = .02).

However, neither smoking status nor smoking intensity was significantly associated with pain sensitization, assessed from the pressure pain threshold at the right wrist, according to the data reported at the meeting, which was sponsored by the Osteoarthritis Research Society International.

“We found smoking was related to knee pain severity and widespread pain, but not with pain sensitization,” Dr. Niu concluded.

“The number of current smokers in our analysis was limited,” she said. In addition, “subjects with knee pain were more likely to be recruited into the MOST study because they have a high risk of developing knee osteoarthritis. This inclusion criterion may lead to selection bias when we study knee pain and other pain-related outcomes.”

One session attendee noted that the confounders in the analyses did not include socioeconomic factors and recommended they be added. “Of course, smoking status could be confounded by socioeconomic factors, and couldn’t it just be that smoking is a surrogate measure?” he asked.

“It’s a good suggestion,” Dr. Niu agreed, noting that the data set has some socioeconomic measures, such as education, that could be incorporated into analyses.

In an interview, Dr. Timothy McAlindon, one of the session’s comoderators and a professor of medicine at Tufts University, Boston, said, “I think this is a very nicely done study looking at the association of smoking with pain in osteoarthritis.

“What they found is there is clearly a significant association of smoking with pain and incident widespread pain. What was less clear was the mechanistic relationship. Maybe they didn’t test the right mechanistic measures,” he proposed.

“If there is a causal relationship, it could perhaps suggest intervention. But I think that is very conjectural based on what they have done so far,” Dr. McAlindon concluded.

Privately insured patients with asthma faced an 81% rise in out-of-pocket costs for albuterol and used slightly less of the medication after the Food and Drug Administration banned chlorofluorocarbon-based inhalers, researchers reported online in JAMA Internal Medicine.

But the ban did not appear to affect rates of hospitalization or emergency department or outpatient visits for asthma, said Dr. Anupam Jena of Massachusetts General Hospital in Boston and his associates. “The impact of the FDA policy on individuals without insurance who faced greater increases in out-of-pocket costs warrants further exploration,” the researchers emphasized.

©BananaStock/thinkstockphotos.com

Concerns about ozone depletion led the FDA in 2005 to announce a ban on CFC inhalers that became effective at the end of 2008. Patients were left with pricier branded hydrofluoroalkane albuterol inhalers, Dr. Jena and his associates noted (JAMA Intern. Med. 2015 May 11 [doi:10.1001/jamainternmed.2015.1665]).

To investigate the economic and clinical effects of this shift, the researchers analyzed private insurance data from 2004 to 2010 on 109,428 adults and 37,281 children with asthma.

The average out-of-pocket cost of an albuterol prescription rose from $13.60 (95% confidence interval, $13.40-$13.70) in 2004 to $25.00 (95% CI, $24.80-$25.20) in 2008, just after the ban went into effect, the researchers reported. By 2010, the average cost of a prescription had dropped to $21.00 (95% CI, $20.80-$21.20). “Steep declines in use of generic CFC inhalers occurred after the fourth quarter of 2006 and were almost fully offset by increases in use of hydrofluoroalkane inhalers,” added the researchers. Furthermore, every $10 increase in out-of-pocket albuterol prescription costs was tied to about a 0.92 percentage point decline in use of the inhalers (95% CI, −1.39 to −0.44; P < .001) in adults, and a 0.54 percentage point in children (95% CI, −0.84 to −0.24; P = .001), they said. Usage did not vary significantly between adults and children or among patients with persistent or nonpersistent asthma, they added.

The National Institutes of Health, National Institute on Aging, and University of Minnesota funded the study. The investigators declared no relevant conflicts of interest.

Privately insured patients with asthma faced an 81% rise in out-of-pocket costs for albuterol and used slightly less of the medication after the Food and Drug Administration banned chlorofluorocarbon-based inhalers, researchers reported online in JAMA Internal Medicine.

But the ban did not appear to affect rates of hospitalization or emergency department or outpatient visits for asthma, said Dr. Anupam Jena of Massachusetts General Hospital in Boston and his associates. “The impact of the FDA policy on individuals without insurance who faced greater increases in out-of-pocket costs warrants further exploration,” the researchers emphasized.

©BananaStock/thinkstockphotos.com

Concerns about ozone depletion led the FDA in 2005 to announce a ban on CFC inhalers that became effective at the end of 2008. Patients were left with pricier branded hydrofluoroalkane albuterol inhalers, Dr. Jena and his associates noted (JAMA Intern. Med. 2015 May 11 [doi:10.1001/jamainternmed.2015.1665]).

To investigate the economic and clinical effects of this shift, the researchers analyzed private insurance data from 2004 to 2010 on 109,428 adults and 37,281 children with asthma.

The average out-of-pocket cost of an albuterol prescription rose from $13.60 (95% confidence interval, $13.40-$13.70) in 2004 to $25.00 (95% CI, $24.80-$25.20) in 2008, just after the ban went into effect, the researchers reported. By 2010, the average cost of a prescription had dropped to $21.00 (95% CI, $20.80-$21.20). “Steep declines in use of generic CFC inhalers occurred after the fourth quarter of 2006 and were almost fully offset by increases in use of hydrofluoroalkane inhalers,” added the researchers. Furthermore, every $10 increase in out-of-pocket albuterol prescription costs was tied to about a 0.92 percentage point decline in use of the inhalers (95% CI, −1.39 to −0.44; P < .001) in adults, and a 0.54 percentage point in children (95% CI, −0.84 to −0.24; P = .001), they said. Usage did not vary significantly between adults and children or among patients with persistent or nonpersistent asthma, they added.

The National Institutes of Health, National Institute on Aging, and University of Minnesota funded the study. The investigators declared no relevant conflicts of interest.

Privately insured patients with asthma faced an 81% rise in out-of-pocket costs for albuterol and used slightly less of the medication after the Food and Drug Administration banned chlorofluorocarbon-based inhalers, researchers reported online in JAMA Internal Medicine.

But the ban did not appear to affect rates of hospitalization or emergency department or outpatient visits for asthma, said Dr. Anupam Jena of Massachusetts General Hospital in Boston and his associates. “The impact of the FDA policy on individuals without insurance who faced greater increases in out-of-pocket costs warrants further exploration,” the researchers emphasized.

©BananaStock/thinkstockphotos.com

Concerns about ozone depletion led the FDA in 2005 to announce a ban on CFC inhalers that became effective at the end of 2008. Patients were left with pricier branded hydrofluoroalkane albuterol inhalers, Dr. Jena and his associates noted (JAMA Intern. Med. 2015 May 11 [doi:10.1001/jamainternmed.2015.1665]).

To investigate the economic and clinical effects of this shift, the researchers analyzed private insurance data from 2004 to 2010 on 109,428 adults and 37,281 children with asthma.

The average out-of-pocket cost of an albuterol prescription rose from $13.60 (95% confidence interval, $13.40-$13.70) in 2004 to $25.00 (95% CI, $24.80-$25.20) in 2008, just after the ban went into effect, the researchers reported. By 2010, the average cost of a prescription had dropped to $21.00 (95% CI, $20.80-$21.20). “Steep declines in use of generic CFC inhalers occurred after the fourth quarter of 2006 and were almost fully offset by increases in use of hydrofluoroalkane inhalers,” added the researchers. Furthermore, every $10 increase in out-of-pocket albuterol prescription costs was tied to about a 0.92 percentage point decline in use of the inhalers (95% CI, −1.39 to −0.44; P < .001) in adults, and a 0.54 percentage point in children (95% CI, −0.84 to −0.24; P = .001), they said. Usage did not vary significantly between adults and children or among patients with persistent or nonpersistent asthma, they added.

The National Institutes of Health, National Institute on Aging, and University of Minnesota funded the study. The investigators declared no relevant conflicts of interest.

SAN DIEGO – Hospitals treating neurologically impaired children with pneumonia typically have the best clinical outcomes, shortest lengths of stay, and lowest readmission rates when fewer diagnostic tests are performed.

This suggests that testing protocols across hospital centers should be standardized so clinicians perform as few testing procedures as possible, thus ensuring an elevated standard of care, said Dr. Joanna E. Thomson, a pediatric hospitalist at the Cincinnati Children’s Hospital Medical Center.

“This population of children accounts for an increasing and disproportionate amount of inpatient hospital resources,” Dr. Thomson said at the annual meeting of the Pediatric Academic Societies. “While they represent just 14% of pediatric admissions, they account for 25% of pediatric hospital days and 30% of pediatric hospital charges.”

As defined by Dr. Thomson and her coinvestigators, neurological impairment (NI) was defined as any “neurologic disease resulting in functional or intellectual impairment,” such as cerebral palsy or epilepsy. Within the population of children with NI, pneumonia is a common reason for intensive care unit admission and the most common cause of death, but diagnostic testing, treatment, and outcomes vary widely from center to center.

After reviewing data on all children aged 1-18 years admitted to one of 40 U.S. children’s hospitals in the Pediatric Health Information Systems (PHIS) database for pneumonia from 2007 to 2012, Dr. Thomson and her associates selected 28,123 subjects for inclusion in the retrospective cohort study. The study had two primary outcomes: assess the variability of diagnostic testing performed at each center and determine the association of hospital-level diagnostic test utilization and hospitalization outcomes, mainly length of stay and 30-day readmission rates.

K-mean clustering was used to divide each hospital center into one of three groups – A, B, or C – based on diagnostic testing habits, with the proportion of patients receiving such testing compared across all included centers. Diagnostic testing was defined as laboratory studies and radiologic imaging ordered within the first 48 hours of admission. Kruskal-Wallis tests were used to compare the outcomes at each hospital.

Hospital centers in group C tended to perform significantly fewer tests than those in groups A and B, Dr. Thomson said.

Complete blood counts were performed on 56% of patients in group C centers, compared with 78% in group A and 72% in group B. Similarly, C-reactive protein tests were administered to 17% of patients in group A, 34% in group B, and 15% in group C. Viral studies were done on 24% of patients in group C, but 44% in group A and 52% in group B. Blood cultures were taken from 44% of patients in group C, but 63% in group A and 66% in group B. Urine culture tests were performed for 9% in group C, 22% of patients in group A, and 17% in group B, she reported.

The only test measured for which group C was not the lowest was respiratory culture: group C centers tested 5% of patients, while those in group A tested 15% and group B only tested 3% of patients.

Length of stay and 30-day readmission rates also were consistently lower for group C than groups A and B. Median length of stay across groups was 3.2 days; no hospital center in group C had a mean length of stay higher than 3.2, compared with 14 centers in group A and 5 in group B. The median 30-day readmission rate was 7.9% across all groups, a rate exceeded by 11 group A centers, 6 group B centers, and only 2 group C centers.

“We found [that] substantial hospital level variation exists in both diagnostic testing and outcomes,” Dr. Thomson said, adding that, since centers performing the fewest tests yielded the best outcomes, the findings here “represent an opportunity to improve the value of care provided to this important pediatric population” and that “overall testing can likely decrease without compromising the care we provide.”

Dr. Thomson did not report any relevant financial disclosures.

[email protected]

SAN DIEGO – Hospitals treating neurologically impaired children with pneumonia typically have the best clinical outcomes, shortest lengths of stay, and lowest readmission rates when fewer diagnostic tests are performed.

This suggests that testing protocols across hospital centers should be standardized so clinicians perform as few testing procedures as possible, thus ensuring an elevated standard of care, said Dr. Joanna E. Thomson, a pediatric hospitalist at the Cincinnati Children’s Hospital Medical Center.

“This population of children accounts for an increasing and disproportionate amount of inpatient hospital resources,” Dr. Thomson said at the annual meeting of the Pediatric Academic Societies. “While they represent just 14% of pediatric admissions, they account for 25% of pediatric hospital days and 30% of pediatric hospital charges.”

As defined by Dr. Thomson and her coinvestigators, neurological impairment (NI) was defined as any “neurologic disease resulting in functional or intellectual impairment,” such as cerebral palsy or epilepsy. Within the population of children with NI, pneumonia is a common reason for intensive care unit admission and the most common cause of death, but diagnostic testing, treatment, and outcomes vary widely from center to center.

After reviewing data on all children aged 1-18 years admitted to one of 40 U.S. children’s hospitals in the Pediatric Health Information Systems (PHIS) database for pneumonia from 2007 to 2012, Dr. Thomson and her associates selected 28,123 subjects for inclusion in the retrospective cohort study. The study had two primary outcomes: assess the variability of diagnostic testing performed at each center and determine the association of hospital-level diagnostic test utilization and hospitalization outcomes, mainly length of stay and 30-day readmission rates.

K-mean clustering was used to divide each hospital center into one of three groups – A, B, or C – based on diagnostic testing habits, with the proportion of patients receiving such testing compared across all included centers. Diagnostic testing was defined as laboratory studies and radiologic imaging ordered within the first 48 hours of admission. Kruskal-Wallis tests were used to compare the outcomes at each hospital.

Hospital centers in group C tended to perform significantly fewer tests than those in groups A and B, Dr. Thomson said.

Complete blood counts were performed on 56% of patients in group C centers, compared with 78% in group A and 72% in group B. Similarly, C-reactive protein tests were administered to 17% of patients in group A, 34% in group B, and 15% in group C. Viral studies were done on 24% of patients in group C, but 44% in group A and 52% in group B. Blood cultures were taken from 44% of patients in group C, but 63% in group A and 66% in group B. Urine culture tests were performed for 9% in group C, 22% of patients in group A, and 17% in group B, she reported.

The only test measured for which group C was not the lowest was respiratory culture: group C centers tested 5% of patients, while those in group A tested 15% and group B only tested 3% of patients.

Length of stay and 30-day readmission rates also were consistently lower for group C than groups A and B. Median length of stay across groups was 3.2 days; no hospital center in group C had a mean length of stay higher than 3.2, compared with 14 centers in group A and 5 in group B. The median 30-day readmission rate was 7.9% across all groups, a rate exceeded by 11 group A centers, 6 group B centers, and only 2 group C centers.

“We found [that] substantial hospital level variation exists in both diagnostic testing and outcomes,” Dr. Thomson said, adding that, since centers performing the fewest tests yielded the best outcomes, the findings here “represent an opportunity to improve the value of care provided to this important pediatric population” and that “overall testing can likely decrease without compromising the care we provide.”

Dr. Thomson did not report any relevant financial disclosures.

[email protected]

SAN DIEGO – Hospitals treating neurologically impaired children with pneumonia typically have the best clinical outcomes, shortest lengths of stay, and lowest readmission rates when fewer diagnostic tests are performed.

This suggests that testing protocols across hospital centers should be standardized so clinicians perform as few testing procedures as possible, thus ensuring an elevated standard of care, said Dr. Joanna E. Thomson, a pediatric hospitalist at the Cincinnati Children’s Hospital Medical Center.

“This population of children accounts for an increasing and disproportionate amount of inpatient hospital resources,” Dr. Thomson said at the annual meeting of the Pediatric Academic Societies. “While they represent just 14% of pediatric admissions, they account for 25% of pediatric hospital days and 30% of pediatric hospital charges.”

As defined by Dr. Thomson and her coinvestigators, neurological impairment (NI) was defined as any “neurologic disease resulting in functional or intellectual impairment,” such as cerebral palsy or epilepsy. Within the population of children with NI, pneumonia is a common reason for intensive care unit admission and the most common cause of death, but diagnostic testing, treatment, and outcomes vary widely from center to center.

After reviewing data on all children aged 1-18 years admitted to one of 40 U.S. children’s hospitals in the Pediatric Health Information Systems (PHIS) database for pneumonia from 2007 to 2012, Dr. Thomson and her associates selected 28,123 subjects for inclusion in the retrospective cohort study. The study had two primary outcomes: assess the variability of diagnostic testing performed at each center and determine the association of hospital-level diagnostic test utilization and hospitalization outcomes, mainly length of stay and 30-day readmission rates.

K-mean clustering was used to divide each hospital center into one of three groups – A, B, or C – based on diagnostic testing habits, with the proportion of patients receiving such testing compared across all included centers. Diagnostic testing was defined as laboratory studies and radiologic imaging ordered within the first 48 hours of admission. Kruskal-Wallis tests were used to compare the outcomes at each hospital.

Hospital centers in group C tended to perform significantly fewer tests than those in groups A and B, Dr. Thomson said.

Complete blood counts were performed on 56% of patients in group C centers, compared with 78% in group A and 72% in group B. Similarly, C-reactive protein tests were administered to 17% of patients in group A, 34% in group B, and 15% in group C. Viral studies were done on 24% of patients in group C, but 44% in group A and 52% in group B. Blood cultures were taken from 44% of patients in group C, but 63% in group A and 66% in group B. Urine culture tests were performed for 9% in group C, 22% of patients in group A, and 17% in group B, she reported.

The only test measured for which group C was not the lowest was respiratory culture: group C centers tested 5% of patients, while those in group A tested 15% and group B only tested 3% of patients.

Length of stay and 30-day readmission rates also were consistently lower for group C than groups A and B. Median length of stay across groups was 3.2 days; no hospital center in group C had a mean length of stay higher than 3.2, compared with 14 centers in group A and 5 in group B. The median 30-day readmission rate was 7.9% across all groups, a rate exceeded by 11 group A centers, 6 group B centers, and only 2 group C centers.

“We found [that] substantial hospital level variation exists in both diagnostic testing and outcomes,” Dr. Thomson said, adding that, since centers performing the fewest tests yielded the best outcomes, the findings here “represent an opportunity to improve the value of care provided to this important pediatric population” and that “overall testing can likely decrease without compromising the care we provide.”

Dr. Thomson did not report any relevant financial disclosures.

[email protected]

GAITHERSBURG, MD.– A fixed-dose combination of ivacaftor, already approved for a cystic fibrosis indication, and lumacaftor will likely be the first drug treatment approved for the most common type of cystic fibrosis, based on a Food and Drug Administration advisory panel’s near unanimous support for approval.

At a meeting May 12, the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 12-1 that the data on the safety and efficacy of the fixed-dose combination of ivacaftor, 250 mg, and lumacaftor, 400 mg, administered twice a day, support approval for treating patients aged 12 years and older with CF who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. About half of patients with CF are F508del homozygous, and if approved, this would be the first treatment that addresses the underlying cause of CF in these patients, according to Vertex Pharmaceuticals, the manufacturer of both drugs.

Lumacaftor “facilitates the processing and trafficking of F508del-CTFR to increase its amount at the cell surface,” while ivacaftor “potentiates the channel-open probability of F508del-CTFR delivered to the cell surface by” lumacaftor, according to Vertex. Ivacaftor (Kalydeco) is a CFTR potentiator approved in January 2012 for treating patients with the G551D mutation, who represent about 4% of patients with CF – its indications have been expanded since that time to include other CFTR gene mutations.

In two phase III studies, the proposed dose and another fixed-dose combination of the two drugs were compared with placebo for 24 weeks in about 1,100 patients homozygous for the F580del mutation who were aged 12 years and over. At 24 weeks, the absolute change in percent-predicted forced expiratory volume in 1 second (ppFEV1) over placebo, the primary efficacy endpoint, was a mean of 2.6% and 3.0% among those treated with the 400 mg/250 mg fixed dose every 12 hours, which were statistically significant changes. In an extension study, the effect was sustained through 48 weeks. There also were reductions in pulmonary exacerbations, improvements in body mass index, and CFQ-R improvements – secondary endpoints that favored the treatment arms, according to the company.

The most common adverse events were typical for patients with CF and similar between the treatment groups. There was an imbalance in respiratory adverse events affecting those on the drug combination (23% vs. almost 14% among those on placebo), but most occurred early in treatment, were generally mild to moderate, and resolved without stopping treatment. Those on the drug combination also had more liver-related serious adverse events (three cases among those on the proposed dose and none among those on placebo).

At the time the phase III studies were being planned, the FDA and the company agreed that an ivacaftor monotherapy arm was not needed and that demonstration of the combination’s superiority over placebo would be adequate to show efficacy. In the phase III studies, however, the combination effect was smaller than expected, and there was no substantial evidence indicating that the efficacy of the combination was greater than that of ivacaftor alone, an issue raised by the FDA reviewers.

Despite the lack of monotherapy arms and the inability to determine the contribution of the individual components to the treatment effects, the panel agreed that the drug combination had been shown to be efficacious and voted 13-0 that the data supported the safety of treatment. Panelists commented that the risks appeared to be minimal and that patients could be monitored for liver function test abnormalities and respiratory function, which were manageable.

Voting in favor of approval, pediatric pulmonologist Dr. Robert Castile, professor of pediatrics at Ohio State University, Columbus, said he was particularly impressed with the lack of decline in FEV₁ over 48 weeks among those treated with the combination “and probably more impressed over the steady increase in BMI over the same period.” He added that he balanced those benefits with what he considered minimal risks with the drug with appropriate monitoring.

If the FDA grants approval, Vertex plans to market the combination product as Orkambi. The FDA usually follows the recommendations of its advisory panels. Panelists were cleared of conflicts before the meeting.

About 30,000 people in the United States have cystic fibrosis, about half of whom are homozygous for the F508del, the most common CF mutation, according to the FDA.

[email protected]

GAITHERSBURG, MD.– A fixed-dose combination of ivacaftor, already approved for a cystic fibrosis indication, and lumacaftor will likely be the first drug treatment approved for the most common type of cystic fibrosis, based on a Food and Drug Administration advisory panel’s near unanimous support for approval.

At a meeting May 12, the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 12-1 that the data on the safety and efficacy of the fixed-dose combination of ivacaftor, 250 mg, and lumacaftor, 400 mg, administered twice a day, support approval for treating patients aged 12 years and older with CF who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. About half of patients with CF are F508del homozygous, and if approved, this would be the first treatment that addresses the underlying cause of CF in these patients, according to Vertex Pharmaceuticals, the manufacturer of both drugs.

Lumacaftor “facilitates the processing and trafficking of F508del-CTFR to increase its amount at the cell surface,” while ivacaftor “potentiates the channel-open probability of F508del-CTFR delivered to the cell surface by” lumacaftor, according to Vertex. Ivacaftor (Kalydeco) is a CFTR potentiator approved in January 2012 for treating patients with the G551D mutation, who represent about 4% of patients with CF – its indications have been expanded since that time to include other CFTR gene mutations.

In two phase III studies, the proposed dose and another fixed-dose combination of the two drugs were compared with placebo for 24 weeks in about 1,100 patients homozygous for the F580del mutation who were aged 12 years and over. At 24 weeks, the absolute change in percent-predicted forced expiratory volume in 1 second (ppFEV1) over placebo, the primary efficacy endpoint, was a mean of 2.6% and 3.0% among those treated with the 400 mg/250 mg fixed dose every 12 hours, which were statistically significant changes. In an extension study, the effect was sustained through 48 weeks. There also were reductions in pulmonary exacerbations, improvements in body mass index, and CFQ-R improvements – secondary endpoints that favored the treatment arms, according to the company.

The most common adverse events were typical for patients with CF and similar between the treatment groups. There was an imbalance in respiratory adverse events affecting those on the drug combination (23% vs. almost 14% among those on placebo), but most occurred early in treatment, were generally mild to moderate, and resolved without stopping treatment. Those on the drug combination also had more liver-related serious adverse events (three cases among those on the proposed dose and none among those on placebo).

At the time the phase III studies were being planned, the FDA and the company agreed that an ivacaftor monotherapy arm was not needed and that demonstration of the combination’s superiority over placebo would be adequate to show efficacy. In the phase III studies, however, the combination effect was smaller than expected, and there was no substantial evidence indicating that the efficacy of the combination was greater than that of ivacaftor alone, an issue raised by the FDA reviewers.

Despite the lack of monotherapy arms and the inability to determine the contribution of the individual components to the treatment effects, the panel agreed that the drug combination had been shown to be efficacious and voted 13-0 that the data supported the safety of treatment. Panelists commented that the risks appeared to be minimal and that patients could be monitored for liver function test abnormalities and respiratory function, which were manageable.

Voting in favor of approval, pediatric pulmonologist Dr. Robert Castile, professor of pediatrics at Ohio State University, Columbus, said he was particularly impressed with the lack of decline in FEV₁ over 48 weeks among those treated with the combination “and probably more impressed over the steady increase in BMI over the same period.” He added that he balanced those benefits with what he considered minimal risks with the drug with appropriate monitoring.

If the FDA grants approval, Vertex plans to market the combination product as Orkambi. The FDA usually follows the recommendations of its advisory panels. Panelists were cleared of conflicts before the meeting.

About 30,000 people in the United States have cystic fibrosis, about half of whom are homozygous for the F508del, the most common CF mutation, according to the FDA.

[email protected]

GAITHERSBURG, MD.– A fixed-dose combination of ivacaftor, already approved for a cystic fibrosis indication, and lumacaftor will likely be the first drug treatment approved for the most common type of cystic fibrosis, based on a Food and Drug Administration advisory panel’s near unanimous support for approval.

At a meeting May 12, the FDA’s Pulmonary-Allergy Drugs Advisory Committee voted 12-1 that the data on the safety and efficacy of the fixed-dose combination of ivacaftor, 250 mg, and lumacaftor, 400 mg, administered twice a day, support approval for treating patients aged 12 years and older with CF who are homozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. About half of patients with CF are F508del homozygous, and if approved, this would be the first treatment that addresses the underlying cause of CF in these patients, according to Vertex Pharmaceuticals, the manufacturer of both drugs.

Lumacaftor “facilitates the processing and trafficking of F508del-CTFR to increase its amount at the cell surface,” while ivacaftor “potentiates the channel-open probability of F508del-CTFR delivered to the cell surface by” lumacaftor, according to Vertex. Ivacaftor (Kalydeco) is a CFTR potentiator approved in January 2012 for treating patients with the G551D mutation, who represent about 4% of patients with CF – its indications have been expanded since that time to include other CFTR gene mutations.

In two phase III studies, the proposed dose and another fixed-dose combination of the two drugs were compared with placebo for 24 weeks in about 1,100 patients homozygous for the F580del mutation who were aged 12 years and over. At 24 weeks, the absolute change in percent-predicted forced expiratory volume in 1 second (ppFEV1) over placebo, the primary efficacy endpoint, was a mean of 2.6% and 3.0% among those treated with the 400 mg/250 mg fixed dose every 12 hours, which were statistically significant changes. In an extension study, the effect was sustained through 48 weeks. There also were reductions in pulmonary exacerbations, improvements in body mass index, and CFQ-R improvements – secondary endpoints that favored the treatment arms, according to the company.

The most common adverse events were typical for patients with CF and similar between the treatment groups. There was an imbalance in respiratory adverse events affecting those on the drug combination (23% vs. almost 14% among those on placebo), but most occurred early in treatment, were generally mild to moderate, and resolved without stopping treatment. Those on the drug combination also had more liver-related serious adverse events (three cases among those on the proposed dose and none among those on placebo).

At the time the phase III studies were being planned, the FDA and the company agreed that an ivacaftor monotherapy arm was not needed and that demonstration of the combination’s superiority over placebo would be adequate to show efficacy. In the phase III studies, however, the combination effect was smaller than expected, and there was no substantial evidence indicating that the efficacy of the combination was greater than that of ivacaftor alone, an issue raised by the FDA reviewers.

Despite the lack of monotherapy arms and the inability to determine the contribution of the individual components to the treatment effects, the panel agreed that the drug combination had been shown to be efficacious and voted 13-0 that the data supported the safety of treatment. Panelists commented that the risks appeared to be minimal and that patients could be monitored for liver function test abnormalities and respiratory function, which were manageable.

Voting in favor of approval, pediatric pulmonologist Dr. Robert Castile, professor of pediatrics at Ohio State University, Columbus, said he was particularly impressed with the lack of decline in FEV₁ over 48 weeks among those treated with the combination “and probably more impressed over the steady increase in BMI over the same period.” He added that he balanced those benefits with what he considered minimal risks with the drug with appropriate monitoring.

If the FDA grants approval, Vertex plans to market the combination product as Orkambi. The FDA usually follows the recommendations of its advisory panels. Panelists were cleared of conflicts before the meeting.

About 30,000 people in the United States have cystic fibrosis, about half of whom are homozygous for the F508del, the most common CF mutation, according to the FDA.

[email protected]

SAN DIEGO – Teens with chronic illnesses who participated in a program that consisted of mind-body principles and peer support demonstrated statistically significant positive changes in physical and mental well-being, anger, tension, and stress, in a pilot study.

“Young people living with serious chronic illnesses must deal not only with the physical effects and uncomfortable symptoms of their conditions, but must also endure significant psychosocial effects,” Dr. Brittany Blockman said in an interview in advance of the annual meeting of the Pediatric Academic Societies. “As we learn more about the impact of stress not only on mental health but also physical health, it will be important to design interventions and programs that address this vital, yet sometimes intangible area of health.”

Mind-body medicine focuses on the ways in which emotional, mental, social, and spiritual factors can directly impact health, said Dr. Blockman, a resident physician for the University of California, San Francisco’s Pediatric Leadership for the Underserved program. “Mind-body skills can enhance an individual’s sense of control and have been demonstrated to lower sympathetic arousal, decrease anxiety, and improve mood. Some examples of these modalities include meditation, mindfulness practices, breath work, yoga, biofeedback, and guided imagery. There is a growing body of literature reporting the positive physical and psychological health benefits of mind-body group interventions in various adult populations living with chronic illnesses, including improvements in quality of life, mood, pain, stress, coping skills, disease progression, and mortality. However, there is limited research exploring similar mind-body and group support interventions in pediatric and adolescent populations.”

Dr. Blockman and her associates enrolled 10 teens aged 13-18 years with chronic illnesses, and their parents, to study the impact of Communitas, a novel program that provides mind-body skills and peer support. Teens and parents met in separate groups 10 times for 2 hours at a time. Each session consisted of meditation, a lesson on guided imagery or some other mind-body technique, an exercise, and group sharing. The National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale, the Profile of Mood States (POMS), the Brief COPE scale, the Mindfulness Attention Awareness Scale (MAAS), the Perceived Stress Scale, and the Resilience Scale were administered before and after the 10 sessions.

The majority of teens (80%) were female; they attended an average of 7.3 sessions. Illnesses represented included juvenile idiopathic arthritis, cerebral palsy, type 1 diabetes, cancer, muscular dystrophy, cystic fibrosis, lung disease, spinal cord injury, and Wegener’s granulomatosis. Of the nine parents who participated, 75% were female; they completed an average of 7.5 sessions.

When Dr. Blockman and her associates compared baseline teen responses with those immediately after the 10-session intervention, they observed statistically significant effects on a number of scales, including the physical well-being subscale of the NIH PROMIS Global Health Scale (a mean increase of 1.56; P = .047); the mental well-being subscale of the NIH PROMIS Global Health Scale (a mean increase of 2.33; P = .025); the anger subscale of the POMS (a mean decrease of .54; P = .039); the tension subscale of the POMS (a mean decrease of .78; P = .006); the distraction/disengagement subscale of the Brief Cope (a mean decrease of .84; P = .035); and the Perceived Stress Scale (a mean decrease of 3.89; P = .005). The results for adults are still being analyzed.

“I was surprised at how willing the adolescents were to participate in the intervention and how engaged they were in the practices that were taught,” Dr. Blockman said. “It is our hope that the results of this study are helpful in thinking about the types of innovative interventions that may be useful in treating, healing, and supporting adolescents living with chronic illness, as well as their family members.”

She acknowledged certain limitations of the study, including the small sample size and the fact that there was no comparison group. “In the future, we plan to test our intervention further in a controlled trial design study, with a larger sample size. Another limitation is we cannot easily evaluate whether our positive results were attributable to the intervention content or the supportive nature of the intervention group. Our qualitative data may help us in teasing this apart.”

Dr. Blockman reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

SAN DIEGO – Teens with chronic illnesses who participated in a program that consisted of mind-body principles and peer support demonstrated statistically significant positive changes in physical and mental well-being, anger, tension, and stress, in a pilot study.

“Young people living with serious chronic illnesses must deal not only with the physical effects and uncomfortable symptoms of their conditions, but must also endure significant psychosocial effects,” Dr. Brittany Blockman said in an interview in advance of the annual meeting of the Pediatric Academic Societies. “As we learn more about the impact of stress not only on mental health but also physical health, it will be important to design interventions and programs that address this vital, yet sometimes intangible area of health.”

Mind-body medicine focuses on the ways in which emotional, mental, social, and spiritual factors can directly impact health, said Dr. Blockman, a resident physician for the University of California, San Francisco’s Pediatric Leadership for the Underserved program. “Mind-body skills can enhance an individual’s sense of control and have been demonstrated to lower sympathetic arousal, decrease anxiety, and improve mood. Some examples of these modalities include meditation, mindfulness practices, breath work, yoga, biofeedback, and guided imagery. There is a growing body of literature reporting the positive physical and psychological health benefits of mind-body group interventions in various adult populations living with chronic illnesses, including improvements in quality of life, mood, pain, stress, coping skills, disease progression, and mortality. However, there is limited research exploring similar mind-body and group support interventions in pediatric and adolescent populations.”

Dr. Blockman and her associates enrolled 10 teens aged 13-18 years with chronic illnesses, and their parents, to study the impact of Communitas, a novel program that provides mind-body skills and peer support. Teens and parents met in separate groups 10 times for 2 hours at a time. Each session consisted of meditation, a lesson on guided imagery or some other mind-body technique, an exercise, and group sharing. The National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale, the Profile of Mood States (POMS), the Brief COPE scale, the Mindfulness Attention Awareness Scale (MAAS), the Perceived Stress Scale, and the Resilience Scale were administered before and after the 10 sessions.

The majority of teens (80%) were female; they attended an average of 7.3 sessions. Illnesses represented included juvenile idiopathic arthritis, cerebral palsy, type 1 diabetes, cancer, muscular dystrophy, cystic fibrosis, lung disease, spinal cord injury, and Wegener’s granulomatosis. Of the nine parents who participated, 75% were female; they completed an average of 7.5 sessions.

When Dr. Blockman and her associates compared baseline teen responses with those immediately after the 10-session intervention, they observed statistically significant effects on a number of scales, including the physical well-being subscale of the NIH PROMIS Global Health Scale (a mean increase of 1.56; P = .047); the mental well-being subscale of the NIH PROMIS Global Health Scale (a mean increase of 2.33; P = .025); the anger subscale of the POMS (a mean decrease of .54; P = .039); the tension subscale of the POMS (a mean decrease of .78; P = .006); the distraction/disengagement subscale of the Brief Cope (a mean decrease of .84; P = .035); and the Perceived Stress Scale (a mean decrease of 3.89; P = .005). The results for adults are still being analyzed.

“I was surprised at how willing the adolescents were to participate in the intervention and how engaged they were in the practices that were taught,” Dr. Blockman said. “It is our hope that the results of this study are helpful in thinking about the types of innovative interventions that may be useful in treating, healing, and supporting adolescents living with chronic illness, as well as their family members.”

She acknowledged certain limitations of the study, including the small sample size and the fact that there was no comparison group. “In the future, we plan to test our intervention further in a controlled trial design study, with a larger sample size. Another limitation is we cannot easily evaluate whether our positive results were attributable to the intervention content or the supportive nature of the intervention group. Our qualitative data may help us in teasing this apart.”

Dr. Blockman reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

SAN DIEGO – Teens with chronic illnesses who participated in a program that consisted of mind-body principles and peer support demonstrated statistically significant positive changes in physical and mental well-being, anger, tension, and stress, in a pilot study.

“Young people living with serious chronic illnesses must deal not only with the physical effects and uncomfortable symptoms of their conditions, but must also endure significant psychosocial effects,” Dr. Brittany Blockman said in an interview in advance of the annual meeting of the Pediatric Academic Societies. “As we learn more about the impact of stress not only on mental health but also physical health, it will be important to design interventions and programs that address this vital, yet sometimes intangible area of health.”

Mind-body medicine focuses on the ways in which emotional, mental, social, and spiritual factors can directly impact health, said Dr. Blockman, a resident physician for the University of California, San Francisco’s Pediatric Leadership for the Underserved program. “Mind-body skills can enhance an individual’s sense of control and have been demonstrated to lower sympathetic arousal, decrease anxiety, and improve mood. Some examples of these modalities include meditation, mindfulness practices, breath work, yoga, biofeedback, and guided imagery. There is a growing body of literature reporting the positive physical and psychological health benefits of mind-body group interventions in various adult populations living with chronic illnesses, including improvements in quality of life, mood, pain, stress, coping skills, disease progression, and mortality. However, there is limited research exploring similar mind-body and group support interventions in pediatric and adolescent populations.”

Dr. Blockman and her associates enrolled 10 teens aged 13-18 years with chronic illnesses, and their parents, to study the impact of Communitas, a novel program that provides mind-body skills and peer support. Teens and parents met in separate groups 10 times for 2 hours at a time. Each session consisted of meditation, a lesson on guided imagery or some other mind-body technique, an exercise, and group sharing. The National Institutes of Health (NIH) Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale, the Profile of Mood States (POMS), the Brief COPE scale, the Mindfulness Attention Awareness Scale (MAAS), the Perceived Stress Scale, and the Resilience Scale were administered before and after the 10 sessions.

The majority of teens (80%) were female; they attended an average of 7.3 sessions. Illnesses represented included juvenile idiopathic arthritis, cerebral palsy, type 1 diabetes, cancer, muscular dystrophy, cystic fibrosis, lung disease, spinal cord injury, and Wegener’s granulomatosis. Of the nine parents who participated, 75% were female; they completed an average of 7.5 sessions.

When Dr. Blockman and her associates compared baseline teen responses with those immediately after the 10-session intervention, they observed statistically significant effects on a number of scales, including the physical well-being subscale of the NIH PROMIS Global Health Scale (a mean increase of 1.56; P = .047); the mental well-being subscale of the NIH PROMIS Global Health Scale (a mean increase of 2.33; P = .025); the anger subscale of the POMS (a mean decrease of .54; P = .039); the tension subscale of the POMS (a mean decrease of .78; P = .006); the distraction/disengagement subscale of the Brief Cope (a mean decrease of .84; P = .035); and the Perceived Stress Scale (a mean decrease of 3.89; P = .005). The results for adults are still being analyzed.

“I was surprised at how willing the adolescents were to participate in the intervention and how engaged they were in the practices that were taught,” Dr. Blockman said. “It is our hope that the results of this study are helpful in thinking about the types of innovative interventions that may be useful in treating, healing, and supporting adolescents living with chronic illness, as well as their family members.”

She acknowledged certain limitations of the study, including the small sample size and the fact that there was no comparison group. “In the future, we plan to test our intervention further in a controlled trial design study, with a larger sample size. Another limitation is we cannot easily evaluate whether our positive results were attributable to the intervention content or the supportive nature of the intervention group. Our qualitative data may help us in teasing this apart.”

Dr. Blockman reported having no relevant financial conflicts.

[email protected]

On Twitter @dougbrunk

SAN DIEGO – Promising developments in the treatment and perhaps even prevention of cystic fibrosis–related diabetes are on the horizon – and they’re coming none too soon.

This is a field in need of a kick start, Dr. Antoinette Moran said at the annual meeting of the Pediatric Academic Societies.

Bruce Jancin/Frontline Medical News

She cited her recent review of 664 cystic fibrosis patients treated at the University of Minnesota during 2008-2012. Overall mortality in those with cystic fibrosis–related diabetes (CFRD) was unchanged from the high rates seen in a similar review covering 2003-2008, despite adoption of an institutional policy of aggressive screening for diabetes and early initiation of insulin therapy upon diagnosis of CFRD (Am. J. Respir. Crit. Care Med. 2015;191:194-200).

“Certainly screening and early institution of insulin are critical, but we seem to have come up against a wall. Honestly, at the University of Minnesota there is no way that we can be more aggressive than we already are with screening and with insulin. We have done as much as we can. So we need to think of something different to move this to the next stage,” said Dr. Moran, professor of pediatrics and chief of the division of pediatric endocrinology and diabetes at the University of Minnesota, Minneapolis.

She highlighted what she considers two of the most promising novel areas of CFRD research. One involves high-priority studies laying the groundwork for possible initiation of insulin therapy in cystic fibrosis (CF) patients even before they are diagnosed with CFRD, possibly starting in infancy.

The other major event is the anticipated Food and Drug Administration approval of a fixed-dose combination of ivacaftor and lumacaftor, a combined potentiator and corrector of the CF transmembrane conductance regulator (CFTR). Mutations in this chloride conduction channel are the most common cause of CF. Marketing approval for the new combination agent, which has breakthrough drug designation, is believed to be imminent.

“This is absolutely fascinating and a real game changer in the world of CF: the ability to fix CFTR, the abnormal CF chloride channel,” Dr. Moran said. “It’s expected that virtually every CF patient in the country is going to be on these drugs once the combination is approved.”

A large multicenter postmarketing study known as PROSPECT is in place and ready to start once the ivacaftor/lumacaftor combination receives approval. It will capture patients right before they start the agent and then follow them longitudinally. Dr. Moran is principal investigator for the GIFT (Gastrointestinal/Glucose and Insulin Functional Testing) substudy of PROSPECT. This 75-patient study will entail oral glucose tolerance testing with insulin, glucose, and C-peptide levels obtained at baseline and 1, 6, and 12 months.

The rationale for GIFT comes from the fact that CFTR mutations are present in the pancreatic beta cells of CF patients. An earlier five-patient pilot study conducted by Dr. Moran suggested ivacaftor might improve insulin secretion in patients with CF. This observation raises the question: “If we could start the drugs in very young children, might it prevent the development of diabetes? If the basic CFTR defect impacts beta cell function, it suggests this is going to be the way to get around that impasse – that treatment other than insulin will prevent or at least partially treat CFRD,” she said.

Another approach to preventing CFRD is being pursued by her colleague, Dr. Katie Larson Ode, a pediatric diabetologist at the University of Iowa, Iowa City. She showed that abnormal glucose tolerance was already present in 41% of 6- to 9-year-olds with CF, and among that subgroup, 42% developed early-onset CFRD at an average age of 11 years in girls and 12 years in boys, in contrast to the general Minnesota CF population, where the average age of onset of CFRD is age 23 years.

Moreover, the 59% of 6- to 9-year-olds with normal glucose tolerance had impaired insulin secretion. Their insulin secretion on oral glucose tolerance testing was half that of controls without CF.

This raises a question: Were these CF children born with these defects, or do the abnormalities evolve slowly during childhood? Dr. Ode is attempting to find out by performing annual oral glucose tolerance tests starting in infancy at the time of CF diagnosis. She is looking prospectively at the relationships between glucose and insulin levels and exocrine function, growth, inflammation, and pulmonary function, with the subjects’ unaffected siblings serving as controls.

“If those infants and toddlers with CF have abnormal insulin secretion and if it correlates with worse clinical parameters, we’re really going to have to consider whether we should be starting insulin right away in these babies. After all, we don’t wait to start vitamin D in CF infants until they develop rickets. We treat everything else preventively – we may need to think about doing that with insulin,” said Dr. Moran.

In her 664-patient review of the University of Minnesota experience with CF during 2008-2012, overall mortality in those with CFRD was 1.8 per 100 person-years ,compared with 0.5 per 100 person-years in CF patients without diabetes. In patients with mild CF genotypes, the risk of mortality was 20% in those with CFRD compared with 2% without diabetes. In patients with severe genotypes, overall mortality was 12% in those with CFRD, threefold higher than in those without diabetes.

Dr. Moran reported having financial relationships with Novo Nordisk and Vertex, which is developing ivacaftor/lumacaftor.

[email protected]

SAN DIEGO – Promising developments in the treatment and perhaps even prevention of cystic fibrosis–related diabetes are on the horizon – and they’re coming none too soon.

This is a field in need of a kick start, Dr. Antoinette Moran said at the annual meeting of the Pediatric Academic Societies.

Bruce Jancin/Frontline Medical News

She cited her recent review of 664 cystic fibrosis patients treated at the University of Minnesota during 2008-2012. Overall mortality in those with cystic fibrosis–related diabetes (CFRD) was unchanged from the high rates seen in a similar review covering 2003-2008, despite adoption of an institutional policy of aggressive screening for diabetes and early initiation of insulin therapy upon diagnosis of CFRD (Am. J. Respir. Crit. Care Med. 2015;191:194-200).

“Certainly screening and early institution of insulin are critical, but we seem to have come up against a wall. Honestly, at the University of Minnesota there is no way that we can be more aggressive than we already are with screening and with insulin. We have done as much as we can. So we need to think of something different to move this to the next stage,” said Dr. Moran, professor of pediatrics and chief of the division of pediatric endocrinology and diabetes at the University of Minnesota, Minneapolis.

She highlighted what she considers two of the most promising novel areas of CFRD research. One involves high-priority studies laying the groundwork for possible initiation of insulin therapy in cystic fibrosis (CF) patients even before they are diagnosed with CFRD, possibly starting in infancy.

The other major event is the anticipated Food and Drug Administration approval of a fixed-dose combination of ivacaftor and lumacaftor, a combined potentiator and corrector of the CF transmembrane conductance regulator (CFTR). Mutations in this chloride conduction channel are the most common cause of CF. Marketing approval for the new combination agent, which has breakthrough drug designation, is believed to be imminent.

“This is absolutely fascinating and a real game changer in the world of CF: the ability to fix CFTR, the abnormal CF chloride channel,” Dr. Moran said. “It’s expected that virtually every CF patient in the country is going to be on these drugs once the combination is approved.”

A large multicenter postmarketing study known as PROSPECT is in place and ready to start once the ivacaftor/lumacaftor combination receives approval. It will capture patients right before they start the agent and then follow them longitudinally. Dr. Moran is principal investigator for the GIFT (Gastrointestinal/Glucose and Insulin Functional Testing) substudy of PROSPECT. This 75-patient study will entail oral glucose tolerance testing with insulin, glucose, and C-peptide levels obtained at baseline and 1, 6, and 12 months.

The rationale for GIFT comes from the fact that CFTR mutations are present in the pancreatic beta cells of CF patients. An earlier five-patient pilot study conducted by Dr. Moran suggested ivacaftor might improve insulin secretion in patients with CF. This observation raises the question: “If we could start the drugs in very young children, might it prevent the development of diabetes? If the basic CFTR defect impacts beta cell function, it suggests this is going to be the way to get around that impasse – that treatment other than insulin will prevent or at least partially treat CFRD,” she said.

Another approach to preventing CFRD is being pursued by her colleague, Dr. Katie Larson Ode, a pediatric diabetologist at the University of Iowa, Iowa City. She showed that abnormal glucose tolerance was already present in 41% of 6- to 9-year-olds with CF, and among that subgroup, 42% developed early-onset CFRD at an average age of 11 years in girls and 12 years in boys, in contrast to the general Minnesota CF population, where the average age of onset of CFRD is age 23 years.

Moreover, the 59% of 6- to 9-year-olds with normal glucose tolerance had impaired insulin secretion. Their insulin secretion on oral glucose tolerance testing was half that of controls without CF.

This raises a question: Were these CF children born with these defects, or do the abnormalities evolve slowly during childhood? Dr. Ode is attempting to find out by performing annual oral glucose tolerance tests starting in infancy at the time of CF diagnosis. She is looking prospectively at the relationships between glucose and insulin levels and exocrine function, growth, inflammation, and pulmonary function, with the subjects’ unaffected siblings serving as controls.

“If those infants and toddlers with CF have abnormal insulin secretion and if it correlates with worse clinical parameters, we’re really going to have to consider whether we should be starting insulin right away in these babies. After all, we don’t wait to start vitamin D in CF infants until they develop rickets. We treat everything else preventively – we may need to think about doing that with insulin,” said Dr. Moran.

In her 664-patient review of the University of Minnesota experience with CF during 2008-2012, overall mortality in those with CFRD was 1.8 per 100 person-years ,compared with 0.5 per 100 person-years in CF patients without diabetes. In patients with mild CF genotypes, the risk of mortality was 20% in those with CFRD compared with 2% without diabetes. In patients with severe genotypes, overall mortality was 12% in those with CFRD, threefold higher than in those without diabetes.

Dr. Moran reported having financial relationships with Novo Nordisk and Vertex, which is developing ivacaftor/lumacaftor.

[email protected]

SAN DIEGO – Promising developments in the treatment and perhaps even prevention of cystic fibrosis–related diabetes are on the horizon – and they’re coming none too soon.

This is a field in need of a kick start, Dr. Antoinette Moran said at the annual meeting of the Pediatric Academic Societies.

Bruce Jancin/Frontline Medical News

She cited her recent review of 664 cystic fibrosis patients treated at the University of Minnesota during 2008-2012. Overall mortality in those with cystic fibrosis–related diabetes (CFRD) was unchanged from the high rates seen in a similar review covering 2003-2008, despite adoption of an institutional policy of aggressive screening for diabetes and early initiation of insulin therapy upon diagnosis of CFRD (Am. J. Respir. Crit. Care Med. 2015;191:194-200).

“Certainly screening and early institution of insulin are critical, but we seem to have come up against a wall. Honestly, at the University of Minnesota there is no way that we can be more aggressive than we already are with screening and with insulin. We have done as much as we can. So we need to think of something different to move this to the next stage,” said Dr. Moran, professor of pediatrics and chief of the division of pediatric endocrinology and diabetes at the University of Minnesota, Minneapolis.

She highlighted what she considers two of the most promising novel areas of CFRD research. One involves high-priority studies laying the groundwork for possible initiation of insulin therapy in cystic fibrosis (CF) patients even before they are diagnosed with CFRD, possibly starting in infancy.

The other major event is the anticipated Food and Drug Administration approval of a fixed-dose combination of ivacaftor and lumacaftor, a combined potentiator and corrector of the CF transmembrane conductance regulator (CFTR). Mutations in this chloride conduction channel are the most common cause of CF. Marketing approval for the new combination agent, which has breakthrough drug designation, is believed to be imminent.

“This is absolutely fascinating and a real game changer in the world of CF: the ability to fix CFTR, the abnormal CF chloride channel,” Dr. Moran said. “It’s expected that virtually every CF patient in the country is going to be on these drugs once the combination is approved.”

A large multicenter postmarketing study known as PROSPECT is in place and ready to start once the ivacaftor/lumacaftor combination receives approval. It will capture patients right before they start the agent and then follow them longitudinally. Dr. Moran is principal investigator for the GIFT (Gastrointestinal/Glucose and Insulin Functional Testing) substudy of PROSPECT. This 75-patient study will entail oral glucose tolerance testing with insulin, glucose, and C-peptide levels obtained at baseline and 1, 6, and 12 months.

The rationale for GIFT comes from the fact that CFTR mutations are present in the pancreatic beta cells of CF patients. An earlier five-patient pilot study conducted by Dr. Moran suggested ivacaftor might improve insulin secretion in patients with CF. This observation raises the question: “If we could start the drugs in very young children, might it prevent the development of diabetes? If the basic CFTR defect impacts beta cell function, it suggests this is going to be the way to get around that impasse – that treatment other than insulin will prevent or at least partially treat CFRD,” she said.

Another approach to preventing CFRD is being pursued by her colleague, Dr. Katie Larson Ode, a pediatric diabetologist at the University of Iowa, Iowa City. She showed that abnormal glucose tolerance was already present in 41% of 6- to 9-year-olds with CF, and among that subgroup, 42% developed early-onset CFRD at an average age of 11 years in girls and 12 years in boys, in contrast to the general Minnesota CF population, where the average age of onset of CFRD is age 23 years.

Moreover, the 59% of 6- to 9-year-olds with normal glucose tolerance had impaired insulin secretion. Their insulin secretion on oral glucose tolerance testing was half that of controls without CF.

This raises a question: Were these CF children born with these defects, or do the abnormalities evolve slowly during childhood? Dr. Ode is attempting to find out by performing annual oral glucose tolerance tests starting in infancy at the time of CF diagnosis. She is looking prospectively at the relationships between glucose and insulin levels and exocrine function, growth, inflammation, and pulmonary function, with the subjects’ unaffected siblings serving as controls.

“If those infants and toddlers with CF have abnormal insulin secretion and if it correlates with worse clinical parameters, we’re really going to have to consider whether we should be starting insulin right away in these babies. After all, we don’t wait to start vitamin D in CF infants until they develop rickets. We treat everything else preventively – we may need to think about doing that with insulin,” said Dr. Moran.

In her 664-patient review of the University of Minnesota experience with CF during 2008-2012, overall mortality in those with CFRD was 1.8 per 100 person-years ,compared with 0.5 per 100 person-years in CF patients without diabetes. In patients with mild CF genotypes, the risk of mortality was 20% in those with CFRD compared with 2% without diabetes. In patients with severe genotypes, overall mortality was 12% in those with CFRD, threefold higher than in those without diabetes.

Dr. Moran reported having financial relationships with Novo Nordisk and Vertex, which is developing ivacaftor/lumacaftor.

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