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Fluoroquinolone bested other antibiotics in Haemophilus influenzae-related pneumonia
WASHINGTON – For adults with Haemophilus influenzae-related community acquired pneumonia, fluoroquinolones were significantly associated with early clinical response rates that were better than those seen with other antibiotics, based on the findings of a German study.
“Initial treatment with any fluoroquinolone was the only positive predictor of early clinical response, and use of macrolide monotherapy was the only negative predictor of early clinical response,” Dr. Christina Forstner, a researcher at the Medical University of Vienna in Austria, said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
The multi-center, observational, prospective, cohort study was conducted between 2002 and 2012 in 171 adults who had community acquired pneumonia and tested positive for H.influenzae. In 124 patients, H.influenzae was the sole pathogen detected, whereas 47 patients had at least one other co-infection.
The primary end point of the study was an early clinical response ‑ clinical stability by day 4 of treatment. The secondary end point was clinical cure anywhere at day 14. The choice of antimicrobial treatment was left to the discretion of individual clinicians.
Early clinical response rates were seen for 46 of 47 patients (97.6%) given any fluoroquinolone, with 100% clinical cure by day 14. Fluoroquinolone monotherapy achieved a nearly 100% early clinical response rate (39 out of 40 patients), and complete clinical cure was seen in all patients by day 14. The rates were significantly different from those seen with other antibiotics (P = .01).
An early clinical response rate was seen in 92 of 108 patients (85.2%) given any beta-lactam. Beta-lactam monotherapy achieved an early clinical response rate in 63 out of 74 cases, with a clinical cure rate at day 14 in 68 out of 74 cases.
An early clinical response rate was seen in 29 of 36 patients (80.6%) who received any macrolide; an early clinical response rate was seen in 8 of 12 patients given monotherapy with a macrolide. Clinical cure rate at day 14 was 32 out of 36 patients given any macrolide, and 11 out of 12 given macrolide monotherapy.
The median duration of therapy was, according to Dr. Forstner, “quite long” at 10 days. Monotherapy was used in 78.4% of patients, and oral treatments in 63.7%.
The overall early clinical response rate was 88%, with an overall clinical cure of 93% on day 14, and of 95.9% on day 28.
A univariate analysis of age, body mass index, severity of disease, co-infection, and treatments used indicated the only factor associated with an early clinical response was the use of any fluoroquinolone (odds ration, 8.8). Macrolide monotherapy was associated with a negative clinical response (OR, 0.239).
As a young physician, I learned to divide my patients with pneumonia into two categories, those with “typical” and those with “atypical” pneumonia. I was taught that different pathogens were the etiology for these two different syndromes, and that I should tailor my antimicrobial treatment appropriately. Later, I learned that our clinical acumen was insufficient to distinguish causative agents in patients with pneumonia.
I therefore now teach residents to partition their pneumonia patients into different demographic categories, such as “community-acquired pneumonia” (CAP) and “health care–associated pneumonia.” Each category is associated with an evidence-based menu of appropriate antimicrobial strategies.
Results from a new German study suggest that, if clinicians know that they are treating CAP due to Haemophilus influenza, outcomes are improved if fluoroquinolones are administered. I wonder, however, how I could be certain early in the clinical course that my patient has pneumonia due to “H Flu”? Do the results apply to other pathogens? Considering that antimicrobial resistance patterns are different in different geographical regions, do these results from Germany apply to my practice in Detroit?
Dr. Daniel Ouellette, FCCP
As a young physician, I learned to divide my patients with pneumonia into two categories, those with “typical” and those with “atypical” pneumonia. I was taught that different pathogens were the etiology for these two different syndromes, and that I should tailor my antimicrobial treatment appropriately. Later, I learned that our clinical acumen was insufficient to distinguish causative agents in patients with pneumonia.
I therefore now teach residents to partition their pneumonia patients into different demographic categories, such as “community-acquired pneumonia” (CAP) and “health care–associated pneumonia.” Each category is associated with an evidence-based menu of appropriate antimicrobial strategies.
Results from a new German study suggest that, if clinicians know that they are treating CAP due to Haemophilus influenza, outcomes are improved if fluoroquinolones are administered. I wonder, however, how I could be certain early in the clinical course that my patient has pneumonia due to “H Flu”? Do the results apply to other pathogens? Considering that antimicrobial resistance patterns are different in different geographical regions, do these results from Germany apply to my practice in Detroit?
Dr. Daniel Ouellette, FCCP
As a young physician, I learned to divide my patients with pneumonia into two categories, those with “typical” and those with “atypical” pneumonia. I was taught that different pathogens were the etiology for these two different syndromes, and that I should tailor my antimicrobial treatment appropriately. Later, I learned that our clinical acumen was insufficient to distinguish causative agents in patients with pneumonia.
I therefore now teach residents to partition their pneumonia patients into different demographic categories, such as “community-acquired pneumonia” (CAP) and “health care–associated pneumonia.” Each category is associated with an evidence-based menu of appropriate antimicrobial strategies.
Results from a new German study suggest that, if clinicians know that they are treating CAP due to Haemophilus influenza, outcomes are improved if fluoroquinolones are administered. I wonder, however, how I could be certain early in the clinical course that my patient has pneumonia due to “H Flu”? Do the results apply to other pathogens? Considering that antimicrobial resistance patterns are different in different geographical regions, do these results from Germany apply to my practice in Detroit?
Dr. Daniel Ouellette, FCCP
WASHINGTON – For adults with Haemophilus influenzae-related community acquired pneumonia, fluoroquinolones were significantly associated with early clinical response rates that were better than those seen with other antibiotics, based on the findings of a German study.
“Initial treatment with any fluoroquinolone was the only positive predictor of early clinical response, and use of macrolide monotherapy was the only negative predictor of early clinical response,” Dr. Christina Forstner, a researcher at the Medical University of Vienna in Austria, said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
The multi-center, observational, prospective, cohort study was conducted between 2002 and 2012 in 171 adults who had community acquired pneumonia and tested positive for H.influenzae. In 124 patients, H.influenzae was the sole pathogen detected, whereas 47 patients had at least one other co-infection.
The primary end point of the study was an early clinical response ‑ clinical stability by day 4 of treatment. The secondary end point was clinical cure anywhere at day 14. The choice of antimicrobial treatment was left to the discretion of individual clinicians.
Early clinical response rates were seen for 46 of 47 patients (97.6%) given any fluoroquinolone, with 100% clinical cure by day 14. Fluoroquinolone monotherapy achieved a nearly 100% early clinical response rate (39 out of 40 patients), and complete clinical cure was seen in all patients by day 14. The rates were significantly different from those seen with other antibiotics (P = .01).
An early clinical response rate was seen in 92 of 108 patients (85.2%) given any beta-lactam. Beta-lactam monotherapy achieved an early clinical response rate in 63 out of 74 cases, with a clinical cure rate at day 14 in 68 out of 74 cases.
An early clinical response rate was seen in 29 of 36 patients (80.6%) who received any macrolide; an early clinical response rate was seen in 8 of 12 patients given monotherapy with a macrolide. Clinical cure rate at day 14 was 32 out of 36 patients given any macrolide, and 11 out of 12 given macrolide monotherapy.
The median duration of therapy was, according to Dr. Forstner, “quite long” at 10 days. Monotherapy was used in 78.4% of patients, and oral treatments in 63.7%.
The overall early clinical response rate was 88%, with an overall clinical cure of 93% on day 14, and of 95.9% on day 28.
A univariate analysis of age, body mass index, severity of disease, co-infection, and treatments used indicated the only factor associated with an early clinical response was the use of any fluoroquinolone (odds ration, 8.8). Macrolide monotherapy was associated with a negative clinical response (OR, 0.239).
WASHINGTON – For adults with Haemophilus influenzae-related community acquired pneumonia, fluoroquinolones were significantly associated with early clinical response rates that were better than those seen with other antibiotics, based on the findings of a German study.
“Initial treatment with any fluoroquinolone was the only positive predictor of early clinical response, and use of macrolide monotherapy was the only negative predictor of early clinical response,” Dr. Christina Forstner, a researcher at the Medical University of Vienna in Austria, said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
The multi-center, observational, prospective, cohort study was conducted between 2002 and 2012 in 171 adults who had community acquired pneumonia and tested positive for H.influenzae. In 124 patients, H.influenzae was the sole pathogen detected, whereas 47 patients had at least one other co-infection.
The primary end point of the study was an early clinical response ‑ clinical stability by day 4 of treatment. The secondary end point was clinical cure anywhere at day 14. The choice of antimicrobial treatment was left to the discretion of individual clinicians.
Early clinical response rates were seen for 46 of 47 patients (97.6%) given any fluoroquinolone, with 100% clinical cure by day 14. Fluoroquinolone monotherapy achieved a nearly 100% early clinical response rate (39 out of 40 patients), and complete clinical cure was seen in all patients by day 14. The rates were significantly different from those seen with other antibiotics (P = .01).
An early clinical response rate was seen in 92 of 108 patients (85.2%) given any beta-lactam. Beta-lactam monotherapy achieved an early clinical response rate in 63 out of 74 cases, with a clinical cure rate at day 14 in 68 out of 74 cases.
An early clinical response rate was seen in 29 of 36 patients (80.6%) who received any macrolide; an early clinical response rate was seen in 8 of 12 patients given monotherapy with a macrolide. Clinical cure rate at day 14 was 32 out of 36 patients given any macrolide, and 11 out of 12 given macrolide monotherapy.
The median duration of therapy was, according to Dr. Forstner, “quite long” at 10 days. Monotherapy was used in 78.4% of patients, and oral treatments in 63.7%.
The overall early clinical response rate was 88%, with an overall clinical cure of 93% on day 14, and of 95.9% on day 28.
A univariate analysis of age, body mass index, severity of disease, co-infection, and treatments used indicated the only factor associated with an early clinical response was the use of any fluoroquinolone (odds ration, 8.8). Macrolide monotherapy was associated with a negative clinical response (OR, 0.239).
AT ICAAC 2014
Key clinical point: Fluoroquinolones may result in better clinical outcomes in adults with community-acquired pneumonia due to Haemophilus influenzae.
Major finding: Early clinical response rates were seen for 46 of 47 patients (97.6%) given any fluoroquinolone, with 100% clinical cure by day 14.
Data source: A German multicenter, observational, prospective cohort study of 171 adults with verified Haemophilus influenzae CAP.
Disclosures: Dr. Forstner said she had no relevant disclosures. The study was made possible through the German CAPNETZ program.
Maternal Tdap resulted in higher maternal cord sera IgG-PT levels
WASHINGTON – Immunizing expectant mothers with the Tdap vaccine booster shot resulted in higher cord serum levels of pertussis toxin antibodies, according to a study from Argentina.
"The results of this study [indicate] that children would be protected from pertussis until they receive the usual immunization schedule," study coauthor Dr. Aurelia Fallo, a researcher at the Hospital de Niños Dr. Ricardo Gutiérrez, Buenos Aires, said in an interview.
The Tdap vaccine for pregnant women was introduced in Argentina in 2012 to help decrease infant morbidity and mortality, according to Dr. Eduardo Lopez, director of pediatric infectious diseases at the hospital, who presented the data during the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
This was the first Latin American study to measure the effect of maternal vaccination with Tdap, he said. Argentina’s recommended schedule for maternal Tdap vaccination is during the third trimester before gestational week 38. Since 2011, the U.S. Centers for Disease Control and Prevention also has recommended that pregnant women receive the Tdap vaccine, after 20 weeks’ gestation.
At a single site in Buenos Aires, Dr. Fallo, Dr. Lopez, and their colleagues took serum samples and maternal cord serum samples at delivery from 88 mothers immunized with the Tdap vaccine. The investigators also took serum samples and maternal cord serum samples at delivery from 108 pairs of non–Tdap-immunized mothers. Serum samples were drawn from 69 nonpregnant women controls as well.
While all of the study participants, including controls, had received their full Tdap vaccination schedules as children, it wasn’t until 2011 that Argentina added the Tdap booster at 11 years of age to the national immunization schedule; therefore, except for the mothers who had received the maternal booster shot, no one in the study had been immunized against pertussis since the age of 6 years, Dr. Fallo said.
In the United States, the Tdap booster is recommended at age 11 years, with Td booster shots to follow every 10 years.
The mean age for all mothers was 26 years. Mothers who received their Tdap booster did so on average at gestational week 25 (standard deviation, 6 weeks).
Each mother/cord sample pair was blinded and measured for IgG-PT (pertussis toxin) antibodies using a validated enzyme-linked immunosorbent assay (ELISA) test. A measurement of 5 EU/mL was considered protective.
The mean concentration of IgG-PT in maternal cord sera taken from vaccinated mothers was 57.2 EU/mL, versus 12.3 EU/mL in unvaccinated mothers (P less than .001).
The mean concentration of IgG-PT in the vaccinated serum samples taken at delivery was 41.1 EU/mL. For the nonimmunized group, the mean IgG-PT concentration was 10.7 EU/mL (P less than .0001).
In the nonimmunized group, 19% had IgG-PT serum levels of less than 5 EU/mL, compared with 2.3% of the mothers who had been immunized (P = .001). Less than 5 EU/mL of IgG-PT was found in 3% of controls (P = .004).
The placenta antibody ratio in immunized mothers was 1.39, versus 1.1 for nonimmunized mothers (P = .01).
According to Dr. Lopez, there was a significant difference for mothers vaccinated before the third trimester, when the mean concentration of IgG-PT was 25.8 EU/mL, compared with the mean 41.9 EU/mL of IgG-PT for mothers in the third trimester (P = .002).
In all, Dr. Lopez said these data indicated that the maternal Tdap vaccination program in Argentina had greatly reduced infant mortality there. "When you compare the mortality rates from 2011 to 2013 in Argentina, there is an 87% reduction," he said. The number of pertussis-related infant deaths went from 76 in 2011 to 10 in 2013, according to official Argentina Ministry of Health records.
"The key point is that maternal Tdap immunization after 20 weeks of gestation seems to be a good strategy to protect infants," Dr. Fallo said.
On Twitter @whitneymcknight
WASHINGTON – Immunizing expectant mothers with the Tdap vaccine booster shot resulted in higher cord serum levels of pertussis toxin antibodies, according to a study from Argentina.
"The results of this study [indicate] that children would be protected from pertussis until they receive the usual immunization schedule," study coauthor Dr. Aurelia Fallo, a researcher at the Hospital de Niños Dr. Ricardo Gutiérrez, Buenos Aires, said in an interview.
The Tdap vaccine for pregnant women was introduced in Argentina in 2012 to help decrease infant morbidity and mortality, according to Dr. Eduardo Lopez, director of pediatric infectious diseases at the hospital, who presented the data during the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
This was the first Latin American study to measure the effect of maternal vaccination with Tdap, he said. Argentina’s recommended schedule for maternal Tdap vaccination is during the third trimester before gestational week 38. Since 2011, the U.S. Centers for Disease Control and Prevention also has recommended that pregnant women receive the Tdap vaccine, after 20 weeks’ gestation.
At a single site in Buenos Aires, Dr. Fallo, Dr. Lopez, and their colleagues took serum samples and maternal cord serum samples at delivery from 88 mothers immunized with the Tdap vaccine. The investigators also took serum samples and maternal cord serum samples at delivery from 108 pairs of non–Tdap-immunized mothers. Serum samples were drawn from 69 nonpregnant women controls as well.
While all of the study participants, including controls, had received their full Tdap vaccination schedules as children, it wasn’t until 2011 that Argentina added the Tdap booster at 11 years of age to the national immunization schedule; therefore, except for the mothers who had received the maternal booster shot, no one in the study had been immunized against pertussis since the age of 6 years, Dr. Fallo said.
In the United States, the Tdap booster is recommended at age 11 years, with Td booster shots to follow every 10 years.
The mean age for all mothers was 26 years. Mothers who received their Tdap booster did so on average at gestational week 25 (standard deviation, 6 weeks).
Each mother/cord sample pair was blinded and measured for IgG-PT (pertussis toxin) antibodies using a validated enzyme-linked immunosorbent assay (ELISA) test. A measurement of 5 EU/mL was considered protective.
The mean concentration of IgG-PT in maternal cord sera taken from vaccinated mothers was 57.2 EU/mL, versus 12.3 EU/mL in unvaccinated mothers (P less than .001).
The mean concentration of IgG-PT in the vaccinated serum samples taken at delivery was 41.1 EU/mL. For the nonimmunized group, the mean IgG-PT concentration was 10.7 EU/mL (P less than .0001).
In the nonimmunized group, 19% had IgG-PT serum levels of less than 5 EU/mL, compared with 2.3% of the mothers who had been immunized (P = .001). Less than 5 EU/mL of IgG-PT was found in 3% of controls (P = .004).
The placenta antibody ratio in immunized mothers was 1.39, versus 1.1 for nonimmunized mothers (P = .01).
According to Dr. Lopez, there was a significant difference for mothers vaccinated before the third trimester, when the mean concentration of IgG-PT was 25.8 EU/mL, compared with the mean 41.9 EU/mL of IgG-PT for mothers in the third trimester (P = .002).
In all, Dr. Lopez said these data indicated that the maternal Tdap vaccination program in Argentina had greatly reduced infant mortality there. "When you compare the mortality rates from 2011 to 2013 in Argentina, there is an 87% reduction," he said. The number of pertussis-related infant deaths went from 76 in 2011 to 10 in 2013, according to official Argentina Ministry of Health records.
"The key point is that maternal Tdap immunization after 20 weeks of gestation seems to be a good strategy to protect infants," Dr. Fallo said.
On Twitter @whitneymcknight
WASHINGTON – Immunizing expectant mothers with the Tdap vaccine booster shot resulted in higher cord serum levels of pertussis toxin antibodies, according to a study from Argentina.
"The results of this study [indicate] that children would be protected from pertussis until they receive the usual immunization schedule," study coauthor Dr. Aurelia Fallo, a researcher at the Hospital de Niños Dr. Ricardo Gutiérrez, Buenos Aires, said in an interview.
The Tdap vaccine for pregnant women was introduced in Argentina in 2012 to help decrease infant morbidity and mortality, according to Dr. Eduardo Lopez, director of pediatric infectious diseases at the hospital, who presented the data during the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
This was the first Latin American study to measure the effect of maternal vaccination with Tdap, he said. Argentina’s recommended schedule for maternal Tdap vaccination is during the third trimester before gestational week 38. Since 2011, the U.S. Centers for Disease Control and Prevention also has recommended that pregnant women receive the Tdap vaccine, after 20 weeks’ gestation.
At a single site in Buenos Aires, Dr. Fallo, Dr. Lopez, and their colleagues took serum samples and maternal cord serum samples at delivery from 88 mothers immunized with the Tdap vaccine. The investigators also took serum samples and maternal cord serum samples at delivery from 108 pairs of non–Tdap-immunized mothers. Serum samples were drawn from 69 nonpregnant women controls as well.
While all of the study participants, including controls, had received their full Tdap vaccination schedules as children, it wasn’t until 2011 that Argentina added the Tdap booster at 11 years of age to the national immunization schedule; therefore, except for the mothers who had received the maternal booster shot, no one in the study had been immunized against pertussis since the age of 6 years, Dr. Fallo said.
In the United States, the Tdap booster is recommended at age 11 years, with Td booster shots to follow every 10 years.
The mean age for all mothers was 26 years. Mothers who received their Tdap booster did so on average at gestational week 25 (standard deviation, 6 weeks).
Each mother/cord sample pair was blinded and measured for IgG-PT (pertussis toxin) antibodies using a validated enzyme-linked immunosorbent assay (ELISA) test. A measurement of 5 EU/mL was considered protective.
The mean concentration of IgG-PT in maternal cord sera taken from vaccinated mothers was 57.2 EU/mL, versus 12.3 EU/mL in unvaccinated mothers (P less than .001).
The mean concentration of IgG-PT in the vaccinated serum samples taken at delivery was 41.1 EU/mL. For the nonimmunized group, the mean IgG-PT concentration was 10.7 EU/mL (P less than .0001).
In the nonimmunized group, 19% had IgG-PT serum levels of less than 5 EU/mL, compared with 2.3% of the mothers who had been immunized (P = .001). Less than 5 EU/mL of IgG-PT was found in 3% of controls (P = .004).
The placenta antibody ratio in immunized mothers was 1.39, versus 1.1 for nonimmunized mothers (P = .01).
According to Dr. Lopez, there was a significant difference for mothers vaccinated before the third trimester, when the mean concentration of IgG-PT was 25.8 EU/mL, compared with the mean 41.9 EU/mL of IgG-PT for mothers in the third trimester (P = .002).
In all, Dr. Lopez said these data indicated that the maternal Tdap vaccination program in Argentina had greatly reduced infant mortality there. "When you compare the mortality rates from 2011 to 2013 in Argentina, there is an 87% reduction," he said. The number of pertussis-related infant deaths went from 76 in 2011 to 10 in 2013, according to official Argentina Ministry of Health records.
"The key point is that maternal Tdap immunization after 20 weeks of gestation seems to be a good strategy to protect infants," Dr. Fallo said.
On Twitter @whitneymcknight
AT ICAAC 2014
Key clinical point: Maternal vaccination with Tdap could help prevent infant pertussis.
Major finding: Mean maternal cord sera levels of IgG-PT in mothers vaccinated with Tdap was 57.2 EU/mL, versus 12.3 EU/mL in unvaccinated mothers (P less than .001).
Data source: Single-site study in Argentina of maternal cord sera from 88 immunized mothers and 108 mothers who were not immunized.
Disclosures: Dr. Fallo and Dr. Lopez said they had no relevant disclosures.
Pathogenic bacteria worsen RSV severity, lengthen ICU stays in infants
WASHINGTON – Potentially pathogenic nasopharyngeal bacterial colonization was associated with more severe respiratory syncytial virus–related bronchiolitis in infants, according to a study.
"We found that [colonization] was significantly more common and almost double in the RSV patients, compared with controls," said Dr. Eleanora Bunsow, a researcher at Nationwide Children’s Hospital in Columbus, Ohio, who presented the data at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. "And RSV patients were frequently colonized with more than one pathogenic bacteria."
Additionally, the use of polymerase chain reaction (PCR) assays to assess bacterial colonization types and levels was found to outperform the accuracy of cultures.
"The PCR showed an increased capacity for bacteria detection and had the ability to quantitate the bacterial load in infant RSV bronchiolitis," Dr. Bunsow said.
While the majority of infants hospitalized with RSV bronchiolitis are previously healthy with no known risk factors, about 15% will require intensive care. The role of pathogenic bacteria has, until recently, been explored only in animal studies, Dr. Bunsow said.
From December 2010 to May 2012, 294 children (median age, 2.5 years) were enrolled at a single site. Of these, 47 were age-matched healthy controls, 182 were inpatient, and 65 were admitted to the ICU. Both inpatient and ICU admissions tended to include twice as many boys as girls (1.6:1 and 1.7:1, respectively). A total of 47% of the control group were African Americans.
Cultures and PCR assays were performed on all study participants for the detection of gram-positive Staphylococcus aureus and Streptococcus pneumoniae, and gram-negative Moraxella catarrhalis and Haemophilus influenzae.
PCR had a 1.4-fold higher level of sensitivity (95% confidence interval, 91%-98%) and equal specificity when compared with cultures for identifying all four bacteria tested.
Polymicrobial bacterial colonization of both gram-positive and gram-negative species was found in 13% of RSV patients, compared with no potentially pathogenic bacterial colonizations in the control group (P = .004).
Rates of colonization were also higher in those with severe RSV infections of the lower respiratory tract who were admitted to the pediatric ICU (PICU), compared with inpatients with less severe disease (53.8% vs. 39%; P = .038). The median clinical disease severity score for those with potentially pathogenic bacterial colonization was 5, compared with a median score of 4 in those without colonization (P = .187).
Colonization with gram-negative bacteria was associated with a "significantly higher" need for up to 3 days of ICU oxygen support, compared with needing only up to 2 days of oxygen for colonization with gram-positive bacteria (P = .039), Dr. Bunsow noted.
Also, H. influenzae was identified in 54% of PICU patients, compared with 39% of inpatient ones. Higher H. influenzae loads correlated with PICU lengths of stay (P = .03).
"Our future study will include outpatients ... and will analyze the impact of the microbiome in these patients," Dr. Bunsow said.
Dr. Bunsow said she had no relevant disclosures.
On Twitter @whitneymcknight
This article highlights an observed association between severe RSV and colonization by pathogenic bacteria. Further investigations into this subgroup of RSV patients for aberrations in their innate immunity would be interesting. The article does not suggest that treatment of the bacteria would positively impact the clinical outcome of the affected patients.
This article highlights an observed association between severe RSV and colonization by pathogenic bacteria. Further investigations into this subgroup of RSV patients for aberrations in their innate immunity would be interesting. The article does not suggest that treatment of the bacteria would positively impact the clinical outcome of the affected patients.
This article highlights an observed association between severe RSV and colonization by pathogenic bacteria. Further investigations into this subgroup of RSV patients for aberrations in their innate immunity would be interesting. The article does not suggest that treatment of the bacteria would positively impact the clinical outcome of the affected patients.
WASHINGTON – Potentially pathogenic nasopharyngeal bacterial colonization was associated with more severe respiratory syncytial virus–related bronchiolitis in infants, according to a study.
"We found that [colonization] was significantly more common and almost double in the RSV patients, compared with controls," said Dr. Eleanora Bunsow, a researcher at Nationwide Children’s Hospital in Columbus, Ohio, who presented the data at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. "And RSV patients were frequently colonized with more than one pathogenic bacteria."
Additionally, the use of polymerase chain reaction (PCR) assays to assess bacterial colonization types and levels was found to outperform the accuracy of cultures.
"The PCR showed an increased capacity for bacteria detection and had the ability to quantitate the bacterial load in infant RSV bronchiolitis," Dr. Bunsow said.
While the majority of infants hospitalized with RSV bronchiolitis are previously healthy with no known risk factors, about 15% will require intensive care. The role of pathogenic bacteria has, until recently, been explored only in animal studies, Dr. Bunsow said.
From December 2010 to May 2012, 294 children (median age, 2.5 years) were enrolled at a single site. Of these, 47 were age-matched healthy controls, 182 were inpatient, and 65 were admitted to the ICU. Both inpatient and ICU admissions tended to include twice as many boys as girls (1.6:1 and 1.7:1, respectively). A total of 47% of the control group were African Americans.
Cultures and PCR assays were performed on all study participants for the detection of gram-positive Staphylococcus aureus and Streptococcus pneumoniae, and gram-negative Moraxella catarrhalis and Haemophilus influenzae.
PCR had a 1.4-fold higher level of sensitivity (95% confidence interval, 91%-98%) and equal specificity when compared with cultures for identifying all four bacteria tested.
Polymicrobial bacterial colonization of both gram-positive and gram-negative species was found in 13% of RSV patients, compared with no potentially pathogenic bacterial colonizations in the control group (P = .004).
Rates of colonization were also higher in those with severe RSV infections of the lower respiratory tract who were admitted to the pediatric ICU (PICU), compared with inpatients with less severe disease (53.8% vs. 39%; P = .038). The median clinical disease severity score for those with potentially pathogenic bacterial colonization was 5, compared with a median score of 4 in those without colonization (P = .187).
Colonization with gram-negative bacteria was associated with a "significantly higher" need for up to 3 days of ICU oxygen support, compared with needing only up to 2 days of oxygen for colonization with gram-positive bacteria (P = .039), Dr. Bunsow noted.
Also, H. influenzae was identified in 54% of PICU patients, compared with 39% of inpatient ones. Higher H. influenzae loads correlated with PICU lengths of stay (P = .03).
"Our future study will include outpatients ... and will analyze the impact of the microbiome in these patients," Dr. Bunsow said.
Dr. Bunsow said she had no relevant disclosures.
On Twitter @whitneymcknight
WASHINGTON – Potentially pathogenic nasopharyngeal bacterial colonization was associated with more severe respiratory syncytial virus–related bronchiolitis in infants, according to a study.
"We found that [colonization] was significantly more common and almost double in the RSV patients, compared with controls," said Dr. Eleanora Bunsow, a researcher at Nationwide Children’s Hospital in Columbus, Ohio, who presented the data at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. "And RSV patients were frequently colonized with more than one pathogenic bacteria."
Additionally, the use of polymerase chain reaction (PCR) assays to assess bacterial colonization types and levels was found to outperform the accuracy of cultures.
"The PCR showed an increased capacity for bacteria detection and had the ability to quantitate the bacterial load in infant RSV bronchiolitis," Dr. Bunsow said.
While the majority of infants hospitalized with RSV bronchiolitis are previously healthy with no known risk factors, about 15% will require intensive care. The role of pathogenic bacteria has, until recently, been explored only in animal studies, Dr. Bunsow said.
From December 2010 to May 2012, 294 children (median age, 2.5 years) were enrolled at a single site. Of these, 47 were age-matched healthy controls, 182 were inpatient, and 65 were admitted to the ICU. Both inpatient and ICU admissions tended to include twice as many boys as girls (1.6:1 and 1.7:1, respectively). A total of 47% of the control group were African Americans.
Cultures and PCR assays were performed on all study participants for the detection of gram-positive Staphylococcus aureus and Streptococcus pneumoniae, and gram-negative Moraxella catarrhalis and Haemophilus influenzae.
PCR had a 1.4-fold higher level of sensitivity (95% confidence interval, 91%-98%) and equal specificity when compared with cultures for identifying all four bacteria tested.
Polymicrobial bacterial colonization of both gram-positive and gram-negative species was found in 13% of RSV patients, compared with no potentially pathogenic bacterial colonizations in the control group (P = .004).
Rates of colonization were also higher in those with severe RSV infections of the lower respiratory tract who were admitted to the pediatric ICU (PICU), compared with inpatients with less severe disease (53.8% vs. 39%; P = .038). The median clinical disease severity score for those with potentially pathogenic bacterial colonization was 5, compared with a median score of 4 in those without colonization (P = .187).
Colonization with gram-negative bacteria was associated with a "significantly higher" need for up to 3 days of ICU oxygen support, compared with needing only up to 2 days of oxygen for colonization with gram-positive bacteria (P = .039), Dr. Bunsow noted.
Also, H. influenzae was identified in 54% of PICU patients, compared with 39% of inpatient ones. Higher H. influenzae loads correlated with PICU lengths of stay (P = .03).
"Our future study will include outpatients ... and will analyze the impact of the microbiome in these patients," Dr. Bunsow said.
Dr. Bunsow said she had no relevant disclosures.
On Twitter @whitneymcknight
AT ICAAC 2014
Key clinical point: Nasopharyngeal colonization with pathogenic bacteria worsens the course of RVS in infants.
Major finding: Polymicrobial bacterial colonization was found in 13% of pediatric patients admitted for RSV, compared with 0% of healthy controls.
Data source: Prospective, single-site study of 247 RSV patients and 47 age-matched healthy controls.
Disclosures: Dr. Bunsow said she had no relevant disclosures.
Novel single-dose flu drug found safe, effective
WASHINGTON – A single injected dose of the neuraminidase inhibitor peramivir safely alleviated flu-like symptoms in adults when administered within 48 hours of onset of illness, an analysis of phase II and phase III clinical trial data indicates.
No single-dose treatment for influenza is currently available in the United States. Approval of the investigational drug would help protect those for whom influenza poses a higher than average risk, such as the elderly, the very young, and those who have other underlying illness such as chronic obstructive pulmonary disease, according to Dr. Richard Whitley, distinguished professor of pediatrics and microbiology at the University of Alabama, Birmingham.
"Historically, we would have said the disease only afflicts [certain populations], but what we learned in the H1N1 pandemic was that ... we can’t ignore influenza. It’s here to stay." He made his comments during a media conference at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
In two placebo-controlled, multicenter studies of a combined 427 adults with acute, uncomplicated influenza, peramivir 300 mg reduced flu symptoms within a median of 22 hours, and resolved fever within 24 hours, compared with placebo (both findings were significant). Symptoms included lethargy, cough, sore throat, headache, and myalgia. Though for time-to-symptom reduction, statistical significance fell away (P = .161), after adjustment for smoking behavior, influenza season, and virus type, the peramivir did significantly reduce nasal viral shedding within 48 hours following treatment, compared with placebo, Dr. Whitley reported
Results were based on patient-reported data using a four-point severity scale recorded over 14 days. Prior to injection, all patients were confirmed to have flu using rapid antigen detection testing, and none had any underlying illnesses or compromised autoimmunity. The drug was administered intramuscularly within 48 hours of onset of illness.
"If you ask me to put that into perspective with the other neuraminidase inhibitors, the level of benefit is virtually identical," said Dr. Whitley.
Currently, only two neuraminidase inhibitors are approved by the Food and Drug Administration: oral oseltamivir and inhaled zanamivir. Both are administered twice daily over 5 days.
Peramivir was determined to be generally safe, well tolerated, and with rates of adverse events such as mild to moderate diarrhea and dizziness similar in both the treatment and placebo arms. A separate study of the drug in a pediatric population is underway, said Dr. William Sheridan, chief medical officer of BioCryst, maker of peramivir.
"Influenza is associated with significant mortality and morbidity," Dr. Whitley said. In addition to annual immunization, "we need antivirals to keep people out of hospitals and to keep people from dying."
Annually, about a quarter million Americans are hospitalized with influenza, and nearly 36,000 die from it, according to the Centers for Disease Control and Prevention.
Peramivir has been approved in Japan and Korea since 2010. If approved by the FDA, it would be the first neuraminidase inhibitor approved in this country in more than a decade.
Pain and practicality
According to Dr. Sheridan, a New Drug Application to the FDA is currently under review with an assigned Prescription Drug User Fee Act action date of December 23, 2014. The indication, if approved, will be for influenza in adults. Dr. Sheridan also spoke during the media briefing.
Dr. Sheridan said that the application to the FDA is for an intravenous infusion that is the bioequivalent of the intramuscular version used in the trials because of the lack of practicality of intramuscular delivery.
"It hurts to get an intramuscular injection. In fact, it hurts a fair bit. We had to have our study subjects lay flat because if you stand up and feel faint after an injection like that, it’s probably a bad thing.
‘Real-world issues’ remain
If approved, the drug could also benefit underserved communities, the panelists agreed.
"If you see the patient once, you’re lucky," said Dr. Whitley. "If you give him a prescription, and you expect him to get it filled, the probability of that happening is maybe 20%-25%. So, if you’re worried about that individual, direct-observed therapy in the health care provider’s office is a good way to help solve this problem."
The shelf life of the drug, according to Dr. Sheridan, is about 5 years, if stored at room temperature.
Because there is less work for the end user, including finding a drug store that has sufficient supplies of the antiviral, "this drug, from a public health perspective, sounds even better than the oral medication," said the media briefing’s host, Dr. Michael Schmidt, professor and vice chair of immunology at the Medical University of South Carolina in Charleston.
"Front-line health care providers should have the availability of the medication so they can treat patients right in the office, without having to worry about filling prescriptions," Dr. Whitley said.
In theory, intravenous peramivir should be "relatively easy for any physician’s office that can handle relatively short IV infusions," according to Dr. Sheridan, who said that physicians would have a choice of using either a butterfly needle on the back of the hand, or an IV cannula in any other accessible vein, infusing the drug in between 15 and 30 minutes.
But questions about what to do if a doctor’s schedule can’t accommodate a patient or if the only access to a provider is through a so-called "minute clinic" are the domain of public health officials.
"There are always these real-world issues, and if there is a pandemic, then public health officials will have to look at the trade-offs," Dr. Schmidt said.
Dr. Whitley reported having no relevant disclosures, but noted that he is on the board of Gilead Sciences, maker of oseltamivir. Dr. Sheridan is the chief medical officer of BioCryst Pharmaceuticals, maker of peramivir. The two international studies were funded by the U.S. Department of Health & Human Services and BioCryst and were conducted at multiple centers in consecutive flu seasons between 2006 and 2008.
On Twitter @whitneymcknight
WASHINGTON – A single injected dose of the neuraminidase inhibitor peramivir safely alleviated flu-like symptoms in adults when administered within 48 hours of onset of illness, an analysis of phase II and phase III clinical trial data indicates.
No single-dose treatment for influenza is currently available in the United States. Approval of the investigational drug would help protect those for whom influenza poses a higher than average risk, such as the elderly, the very young, and those who have other underlying illness such as chronic obstructive pulmonary disease, according to Dr. Richard Whitley, distinguished professor of pediatrics and microbiology at the University of Alabama, Birmingham.
"Historically, we would have said the disease only afflicts [certain populations], but what we learned in the H1N1 pandemic was that ... we can’t ignore influenza. It’s here to stay." He made his comments during a media conference at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
In two placebo-controlled, multicenter studies of a combined 427 adults with acute, uncomplicated influenza, peramivir 300 mg reduced flu symptoms within a median of 22 hours, and resolved fever within 24 hours, compared with placebo (both findings were significant). Symptoms included lethargy, cough, sore throat, headache, and myalgia. Though for time-to-symptom reduction, statistical significance fell away (P = .161), after adjustment for smoking behavior, influenza season, and virus type, the peramivir did significantly reduce nasal viral shedding within 48 hours following treatment, compared with placebo, Dr. Whitley reported
Results were based on patient-reported data using a four-point severity scale recorded over 14 days. Prior to injection, all patients were confirmed to have flu using rapid antigen detection testing, and none had any underlying illnesses or compromised autoimmunity. The drug was administered intramuscularly within 48 hours of onset of illness.
"If you ask me to put that into perspective with the other neuraminidase inhibitors, the level of benefit is virtually identical," said Dr. Whitley.
Currently, only two neuraminidase inhibitors are approved by the Food and Drug Administration: oral oseltamivir and inhaled zanamivir. Both are administered twice daily over 5 days.
Peramivir was determined to be generally safe, well tolerated, and with rates of adverse events such as mild to moderate diarrhea and dizziness similar in both the treatment and placebo arms. A separate study of the drug in a pediatric population is underway, said Dr. William Sheridan, chief medical officer of BioCryst, maker of peramivir.
"Influenza is associated with significant mortality and morbidity," Dr. Whitley said. In addition to annual immunization, "we need antivirals to keep people out of hospitals and to keep people from dying."
Annually, about a quarter million Americans are hospitalized with influenza, and nearly 36,000 die from it, according to the Centers for Disease Control and Prevention.
Peramivir has been approved in Japan and Korea since 2010. If approved by the FDA, it would be the first neuraminidase inhibitor approved in this country in more than a decade.
Pain and practicality
According to Dr. Sheridan, a New Drug Application to the FDA is currently under review with an assigned Prescription Drug User Fee Act action date of December 23, 2014. The indication, if approved, will be for influenza in adults. Dr. Sheridan also spoke during the media briefing.
Dr. Sheridan said that the application to the FDA is for an intravenous infusion that is the bioequivalent of the intramuscular version used in the trials because of the lack of practicality of intramuscular delivery.
"It hurts to get an intramuscular injection. In fact, it hurts a fair bit. We had to have our study subjects lay flat because if you stand up and feel faint after an injection like that, it’s probably a bad thing.
‘Real-world issues’ remain
If approved, the drug could also benefit underserved communities, the panelists agreed.
"If you see the patient once, you’re lucky," said Dr. Whitley. "If you give him a prescription, and you expect him to get it filled, the probability of that happening is maybe 20%-25%. So, if you’re worried about that individual, direct-observed therapy in the health care provider’s office is a good way to help solve this problem."
The shelf life of the drug, according to Dr. Sheridan, is about 5 years, if stored at room temperature.
Because there is less work for the end user, including finding a drug store that has sufficient supplies of the antiviral, "this drug, from a public health perspective, sounds even better than the oral medication," said the media briefing’s host, Dr. Michael Schmidt, professor and vice chair of immunology at the Medical University of South Carolina in Charleston.
"Front-line health care providers should have the availability of the medication so they can treat patients right in the office, without having to worry about filling prescriptions," Dr. Whitley said.
In theory, intravenous peramivir should be "relatively easy for any physician’s office that can handle relatively short IV infusions," according to Dr. Sheridan, who said that physicians would have a choice of using either a butterfly needle on the back of the hand, or an IV cannula in any other accessible vein, infusing the drug in between 15 and 30 minutes.
But questions about what to do if a doctor’s schedule can’t accommodate a patient or if the only access to a provider is through a so-called "minute clinic" are the domain of public health officials.
"There are always these real-world issues, and if there is a pandemic, then public health officials will have to look at the trade-offs," Dr. Schmidt said.
Dr. Whitley reported having no relevant disclosures, but noted that he is on the board of Gilead Sciences, maker of oseltamivir. Dr. Sheridan is the chief medical officer of BioCryst Pharmaceuticals, maker of peramivir. The two international studies were funded by the U.S. Department of Health & Human Services and BioCryst and were conducted at multiple centers in consecutive flu seasons between 2006 and 2008.
On Twitter @whitneymcknight
WASHINGTON – A single injected dose of the neuraminidase inhibitor peramivir safely alleviated flu-like symptoms in adults when administered within 48 hours of onset of illness, an analysis of phase II and phase III clinical trial data indicates.
No single-dose treatment for influenza is currently available in the United States. Approval of the investigational drug would help protect those for whom influenza poses a higher than average risk, such as the elderly, the very young, and those who have other underlying illness such as chronic obstructive pulmonary disease, according to Dr. Richard Whitley, distinguished professor of pediatrics and microbiology at the University of Alabama, Birmingham.
"Historically, we would have said the disease only afflicts [certain populations], but what we learned in the H1N1 pandemic was that ... we can’t ignore influenza. It’s here to stay." He made his comments during a media conference at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
In two placebo-controlled, multicenter studies of a combined 427 adults with acute, uncomplicated influenza, peramivir 300 mg reduced flu symptoms within a median of 22 hours, and resolved fever within 24 hours, compared with placebo (both findings were significant). Symptoms included lethargy, cough, sore throat, headache, and myalgia. Though for time-to-symptom reduction, statistical significance fell away (P = .161), after adjustment for smoking behavior, influenza season, and virus type, the peramivir did significantly reduce nasal viral shedding within 48 hours following treatment, compared with placebo, Dr. Whitley reported
Results were based on patient-reported data using a four-point severity scale recorded over 14 days. Prior to injection, all patients were confirmed to have flu using rapid antigen detection testing, and none had any underlying illnesses or compromised autoimmunity. The drug was administered intramuscularly within 48 hours of onset of illness.
"If you ask me to put that into perspective with the other neuraminidase inhibitors, the level of benefit is virtually identical," said Dr. Whitley.
Currently, only two neuraminidase inhibitors are approved by the Food and Drug Administration: oral oseltamivir and inhaled zanamivir. Both are administered twice daily over 5 days.
Peramivir was determined to be generally safe, well tolerated, and with rates of adverse events such as mild to moderate diarrhea and dizziness similar in both the treatment and placebo arms. A separate study of the drug in a pediatric population is underway, said Dr. William Sheridan, chief medical officer of BioCryst, maker of peramivir.
"Influenza is associated with significant mortality and morbidity," Dr. Whitley said. In addition to annual immunization, "we need antivirals to keep people out of hospitals and to keep people from dying."
Annually, about a quarter million Americans are hospitalized with influenza, and nearly 36,000 die from it, according to the Centers for Disease Control and Prevention.
Peramivir has been approved in Japan and Korea since 2010. If approved by the FDA, it would be the first neuraminidase inhibitor approved in this country in more than a decade.
Pain and practicality
According to Dr. Sheridan, a New Drug Application to the FDA is currently under review with an assigned Prescription Drug User Fee Act action date of December 23, 2014. The indication, if approved, will be for influenza in adults. Dr. Sheridan also spoke during the media briefing.
Dr. Sheridan said that the application to the FDA is for an intravenous infusion that is the bioequivalent of the intramuscular version used in the trials because of the lack of practicality of intramuscular delivery.
"It hurts to get an intramuscular injection. In fact, it hurts a fair bit. We had to have our study subjects lay flat because if you stand up and feel faint after an injection like that, it’s probably a bad thing.
‘Real-world issues’ remain
If approved, the drug could also benefit underserved communities, the panelists agreed.
"If you see the patient once, you’re lucky," said Dr. Whitley. "If you give him a prescription, and you expect him to get it filled, the probability of that happening is maybe 20%-25%. So, if you’re worried about that individual, direct-observed therapy in the health care provider’s office is a good way to help solve this problem."
The shelf life of the drug, according to Dr. Sheridan, is about 5 years, if stored at room temperature.
Because there is less work for the end user, including finding a drug store that has sufficient supplies of the antiviral, "this drug, from a public health perspective, sounds even better than the oral medication," said the media briefing’s host, Dr. Michael Schmidt, professor and vice chair of immunology at the Medical University of South Carolina in Charleston.
"Front-line health care providers should have the availability of the medication so they can treat patients right in the office, without having to worry about filling prescriptions," Dr. Whitley said.
In theory, intravenous peramivir should be "relatively easy for any physician’s office that can handle relatively short IV infusions," according to Dr. Sheridan, who said that physicians would have a choice of using either a butterfly needle on the back of the hand, or an IV cannula in any other accessible vein, infusing the drug in between 15 and 30 minutes.
But questions about what to do if a doctor’s schedule can’t accommodate a patient or if the only access to a provider is through a so-called "minute clinic" are the domain of public health officials.
"There are always these real-world issues, and if there is a pandemic, then public health officials will have to look at the trade-offs," Dr. Schmidt said.
Dr. Whitley reported having no relevant disclosures, but noted that he is on the board of Gilead Sciences, maker of oseltamivir. Dr. Sheridan is the chief medical officer of BioCryst Pharmaceuticals, maker of peramivir. The two international studies were funded by the U.S. Department of Health & Human Services and BioCryst and were conducted at multiple centers in consecutive flu seasons between 2006 and 2008.
On Twitter @whitneymcknight
AT ICAAC 2014
Key clinical point: A single-dose flu treatment could be on the way.
Major finding: Single-dose injectable neuraminidase inhibitor reduced median time to abatement of flu-like symptoms by 22 hours, compared with placebo.
Data source: Retrospective analysis of placebo-controlled data from phase II and phase III studies of a combined 427 adults given a single dose of intramuscular neuraminidase inhibitor within 48 hours of onset of flu-like symptoms (P less than .005). The studies were conducted at multiple centers in consecutive flu seasons between 2006 and 2008
Disclosures: Dr. Whitley said he had no relevant disclosures, but noted that he is on the board of Gilead Sciences, maker of oseltamivir. Dr. Sheridan is the chief medical officer of BioCryst Pharmaceuticals, maker of peramivir. The two international studies were funded by the U.S. Department of Health & Human Services and BioCryst.
May-July epidemic of RSV highest in infants, study shows
WASHINGTON – Respiratory syncytial virus followed an epidemic pattern, particularly in infants, from May through July across 13 years, a study has shown.
The virus also was found more often in infants less than 3 months old who had bronchiolitis or hypoxemia at time of hospital admission, according to Dr. Maria F. Lucion, who presented the data during the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
"This is a really valuable study with a very large number of cases. We don’t have a lot of information on this virus." Dr. Keith Klugman, director of global health at the Bill and Melinda Gates Foundation, Seattle, said during the discussion after the presentation.
From March 2000 to November 2013, 12,555 patients admitted for suspected acute lower respiratory infections to a single center in Argentina were tested for respiratory syncytial virus (RSV), adenovirus, influenza, and parainfluenza using either assays of nasopharyngeal aspirates or real-time polymerase chain reaction.
Of the 4,798 patients who tested positive for infection, 3,924 of all those admitted were found to have RSV (ranging between 71% and 82% across the years), with an annual seasonal epidemic pattern in evidence from May through July.
Independent predictors of RSV included being 3 months or younger (odds ratio 2.8, P less than .01); having bronchiolitis as a clinical presentation (OR 1.54, P less than .01); and the presence of hypoxemia at time of admission (OR 1.84, P less than .01), said Dr. Lucion of Ricardo Gutierrez Children’s Hospital, Buenos Aires.
The overall hospitalization rate for those with bronchiolitis was 39 per 1,000, with a peak in 2003 of 48 per 1,000. Bronchiolitis as a result of RSV was diagnosed in a median 15 patients per 1,000 (8.0-19.4).
The majority of admissions were male (56%), and the median age was 7 months, although nearly half (43%) were less than 6 months old (74.2% were less than 1 year old). Bronchiolitis occurred 61% of the time, and the nosocomial infection rate was 6.6%. The mortality rate was just under 2% (74/3,888).
"The most frequent complication was respiratory distress requiring the use of a ventilator," Dr. Lucion said. "That was most associated with the children who died."
An additional genetic analysis indicated that RSV subtypes A and B were in the pediatric population, with the exceptions of 2000 when only subtype A was present, and 2005, when only subtype B was present.
"The most common genotypes were GA2, GA5, ON1, and NA1 for subtype A and genotype-BA for subtype B," Dr. Lucion said.
Dr. Lucion said she had no relevant disclosures.
On Twitter @whitneymcknight
WASHINGTON – Respiratory syncytial virus followed an epidemic pattern, particularly in infants, from May through July across 13 years, a study has shown.
The virus also was found more often in infants less than 3 months old who had bronchiolitis or hypoxemia at time of hospital admission, according to Dr. Maria F. Lucion, who presented the data during the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
"This is a really valuable study with a very large number of cases. We don’t have a lot of information on this virus." Dr. Keith Klugman, director of global health at the Bill and Melinda Gates Foundation, Seattle, said during the discussion after the presentation.
From March 2000 to November 2013, 12,555 patients admitted for suspected acute lower respiratory infections to a single center in Argentina were tested for respiratory syncytial virus (RSV), adenovirus, influenza, and parainfluenza using either assays of nasopharyngeal aspirates or real-time polymerase chain reaction.
Of the 4,798 patients who tested positive for infection, 3,924 of all those admitted were found to have RSV (ranging between 71% and 82% across the years), with an annual seasonal epidemic pattern in evidence from May through July.
Independent predictors of RSV included being 3 months or younger (odds ratio 2.8, P less than .01); having bronchiolitis as a clinical presentation (OR 1.54, P less than .01); and the presence of hypoxemia at time of admission (OR 1.84, P less than .01), said Dr. Lucion of Ricardo Gutierrez Children’s Hospital, Buenos Aires.
The overall hospitalization rate for those with bronchiolitis was 39 per 1,000, with a peak in 2003 of 48 per 1,000. Bronchiolitis as a result of RSV was diagnosed in a median 15 patients per 1,000 (8.0-19.4).
The majority of admissions were male (56%), and the median age was 7 months, although nearly half (43%) were less than 6 months old (74.2% were less than 1 year old). Bronchiolitis occurred 61% of the time, and the nosocomial infection rate was 6.6%. The mortality rate was just under 2% (74/3,888).
"The most frequent complication was respiratory distress requiring the use of a ventilator," Dr. Lucion said. "That was most associated with the children who died."
An additional genetic analysis indicated that RSV subtypes A and B were in the pediatric population, with the exceptions of 2000 when only subtype A was present, and 2005, when only subtype B was present.
"The most common genotypes were GA2, GA5, ON1, and NA1 for subtype A and genotype-BA for subtype B," Dr. Lucion said.
Dr. Lucion said she had no relevant disclosures.
On Twitter @whitneymcknight
WASHINGTON – Respiratory syncytial virus followed an epidemic pattern, particularly in infants, from May through July across 13 years, a study has shown.
The virus also was found more often in infants less than 3 months old who had bronchiolitis or hypoxemia at time of hospital admission, according to Dr. Maria F. Lucion, who presented the data during the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.
"This is a really valuable study with a very large number of cases. We don’t have a lot of information on this virus." Dr. Keith Klugman, director of global health at the Bill and Melinda Gates Foundation, Seattle, said during the discussion after the presentation.
From March 2000 to November 2013, 12,555 patients admitted for suspected acute lower respiratory infections to a single center in Argentina were tested for respiratory syncytial virus (RSV), adenovirus, influenza, and parainfluenza using either assays of nasopharyngeal aspirates or real-time polymerase chain reaction.
Of the 4,798 patients who tested positive for infection, 3,924 of all those admitted were found to have RSV (ranging between 71% and 82% across the years), with an annual seasonal epidemic pattern in evidence from May through July.
Independent predictors of RSV included being 3 months or younger (odds ratio 2.8, P less than .01); having bronchiolitis as a clinical presentation (OR 1.54, P less than .01); and the presence of hypoxemia at time of admission (OR 1.84, P less than .01), said Dr. Lucion of Ricardo Gutierrez Children’s Hospital, Buenos Aires.
The overall hospitalization rate for those with bronchiolitis was 39 per 1,000, with a peak in 2003 of 48 per 1,000. Bronchiolitis as a result of RSV was diagnosed in a median 15 patients per 1,000 (8.0-19.4).
The majority of admissions were male (56%), and the median age was 7 months, although nearly half (43%) were less than 6 months old (74.2% were less than 1 year old). Bronchiolitis occurred 61% of the time, and the nosocomial infection rate was 6.6%. The mortality rate was just under 2% (74/3,888).
"The most frequent complication was respiratory distress requiring the use of a ventilator," Dr. Lucion said. "That was most associated with the children who died."
An additional genetic analysis indicated that RSV subtypes A and B were in the pediatric population, with the exceptions of 2000 when only subtype A was present, and 2005, when only subtype B was present.
"The most common genotypes were GA2, GA5, ON1, and NA1 for subtype A and genotype-BA for subtype B," Dr. Lucion said.
Dr. Lucion said she had no relevant disclosures.
On Twitter @whitneymcknight
AT ICAAC 2014
Key clinical point: Infants less than 3 months old who had RSV tended to present with bronchiolitis or hypoxemia at the time of admission.
Major finding: Forty-three percent of patients with acute lower respiratory infection who tested positive for the respiratory syncytial virus were infants under the age of 7 months, with highest rates occurring May through July (P less than .001).
Data source: A prospective cohort study of 12,555 patients in Argentina admitted for acute lower respiratory infection between 2000 and 2013.
Disclosures: Dr. Lucion said she had no relevant disclosures.
VIDEO: Access to mental health care a ‘civil rights’ issue
WASHINGTON – Laws that mandate mental illness should be covered by insurance in the same way as any other illness should be viewed on par with the Civil Rights Act, and they should be enforced with the same dedication, according to the former federal lawmaker who authored the Mental Health Parity and Addiction Equity Act of 2008.
Biases against mental illness are built into society at virtually every level, former U.S. Rep. Patrick J. Kennedy (D-R.I.) noted. Although it’s important to "avoid pathologizing" the human experience, he added, recognizing that mental illness affects all Americans at some level will not only save money, but will also make the nation healthier overall.
In a video interview at the annual meeting of the National Alliance on Mental Illness, Mr. Kennedy also shared what he believes are the necessary tools to start – and finish – a health care revolution, tools that already exist or are soon to be developed.
On Twitter @whitneymcknight
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Laws that mandate mental illness should be covered by insurance in the same way as any other illness should be viewed on par with the Civil Rights Act, and they should be enforced with the same dedication, according to the former federal lawmaker who authored the Mental Health Parity and Addiction Equity Act of 2008.
Biases against mental illness are built into society at virtually every level, former U.S. Rep. Patrick J. Kennedy (D-R.I.) noted. Although it’s important to "avoid pathologizing" the human experience, he added, recognizing that mental illness affects all Americans at some level will not only save money, but will also make the nation healthier overall.
In a video interview at the annual meeting of the National Alliance on Mental Illness, Mr. Kennedy also shared what he believes are the necessary tools to start – and finish – a health care revolution, tools that already exist or are soon to be developed.
On Twitter @whitneymcknight
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
WASHINGTON – Laws that mandate mental illness should be covered by insurance in the same way as any other illness should be viewed on par with the Civil Rights Act, and they should be enforced with the same dedication, according to the former federal lawmaker who authored the Mental Health Parity and Addiction Equity Act of 2008.
Biases against mental illness are built into society at virtually every level, former U.S. Rep. Patrick J. Kennedy (D-R.I.) noted. Although it’s important to "avoid pathologizing" the human experience, he added, recognizing that mental illness affects all Americans at some level will not only save money, but will also make the nation healthier overall.
In a video interview at the annual meeting of the National Alliance on Mental Illness, Mr. Kennedy also shared what he believes are the necessary tools to start – and finish – a health care revolution, tools that already exist or are soon to be developed.
On Twitter @whitneymcknight
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE NAMI ANNUAL MEETING
CDC: Time is running out to contain Ebola virus
Despite some signs of hope, the "window of opportunity" to contain and end the current Ebola virus outbreak in West Africa is shutting, causing the situation to worsen "significantly," according to officials at the Centers for Disease Control and Prevention.
"This is really the first epidemic of Ebola the world has ever known," Dr. Thomas Frieden, CDC director, said during a media briefing.
The prevailing belief, according to Dr. Frieden, is that the virus’s rapid spread is not due to mutation but instead to cultural and logistical obstacles.
"It’s not spreading in new ways, according to everything that we know," Dr. Frieden said. "It’s spreading through just two routes: people caring for other people ... and unsafe burial practices. ... That is really the Achilles’ heel. We know how it spreads; we know how to stop it. The challenge is to do that everywhere it is needed."
The Ebola virus is transmitted primarily through body fluids, but it also can be spread through contact with contaminated objects such as needles. Ebola is not spread through the air or by water.
Noting that rapid response is essential, and that data are lacking as to the actual numbers of those infected with the virus, Dr. Frieden outlined three key things that are needed to stem the epidemic: more resources; technical expertise in both health care management and logistics; and a coordinated global approach to ending the outbreak.
Dr. Frieden said it was a paradox that "the more the world isolates these countries, the harder it will be for them to control these outbreaks, the more cases there will be, and the less safe other countries will be. Like it or not, we’re connected."
The area currently experiencing outbreaks includes the countries of Guinea, Liberia, Sierra Leone, and Nigeria, with what Dr. Frieden said is a "dense, forested region that is the epicenter" located where the borders of all but Nigeria meet. The remote area is not serviced by radio or television and is rife with what Dr. Frieden called "misconceptions" about how the disease is transmitted.
"We can turn this around. Sometimes the problem can seem so large, it’s hard to get started, but we can chip away at the challenges, one by one," he said, inviting anyone with experience working in austere conditions, either as a health care provider or manager of an under-resourced facility, to consider volunteering his or her services, noting that the longer the crisis continues, the less stable the local communities will be.
In addition to nearly $20 million in aid from the U.S. Agency for International Development, for goods ranging from personal protection gear to resources for safer burials, the CDC will continue to support efforts by the World Health Organization (WHO) to contain the epidemic within the year, by deploying top CDC epidemic intelligence teams to help with tracking, treatment, and screening, he said.
The need for global coordination is not due to a lack of willingness from local officials and personnel to respond, according to Dr. Frieden.
"The countries are willing. In an Ebola treatment unit run by Doctors Without Borders, more than 90% of the staff are locals," Dr. Frieden said of one of the stops on his tour of West Africa. "Each of the presidents [of the affected countries] said the same thing to me: ‘Tell us what to do and we will do it. If we can’t do it, help us to do it. Teach us to care for Ebola patients and to manage the system more effectively.’ They need the world to work with them."
According to WHO, more than 1,400 patients have died of Ebola virus infection to date in this outbreak, making this the largest Ebola outbreak ever recorded. There are still "significant gaps in reporting in some intense transmission areas," and that the number of cases ultimately may top 20,000, according to WHO, which noted this outbreak has featured the infection and deaths of "an unprecedented number of health care workers."
There are no vaccines for Ebola approved by the Food and Drug Administration, although the National Institute of Allergy and Infectious Diseases currently is attempting to develop one.
As to treatments, ZMapp, a trio of monoclonal antibodies that was successfully used to treat two American health workers who were infected with Ebola, also has shown promise in a controlled trial with primates. According to ZMapp’s manufacturer, Mapp Biopharmaceuticals, the supply of the drug is currently exhausted and there is as yet no date for when more will be available.
On Twitter @whitneymcknight
Despite some signs of hope, the "window of opportunity" to contain and end the current Ebola virus outbreak in West Africa is shutting, causing the situation to worsen "significantly," according to officials at the Centers for Disease Control and Prevention.
"This is really the first epidemic of Ebola the world has ever known," Dr. Thomas Frieden, CDC director, said during a media briefing.
The prevailing belief, according to Dr. Frieden, is that the virus’s rapid spread is not due to mutation but instead to cultural and logistical obstacles.
"It’s not spreading in new ways, according to everything that we know," Dr. Frieden said. "It’s spreading through just two routes: people caring for other people ... and unsafe burial practices. ... That is really the Achilles’ heel. We know how it spreads; we know how to stop it. The challenge is to do that everywhere it is needed."
The Ebola virus is transmitted primarily through body fluids, but it also can be spread through contact with contaminated objects such as needles. Ebola is not spread through the air or by water.
Noting that rapid response is essential, and that data are lacking as to the actual numbers of those infected with the virus, Dr. Frieden outlined three key things that are needed to stem the epidemic: more resources; technical expertise in both health care management and logistics; and a coordinated global approach to ending the outbreak.
Dr. Frieden said it was a paradox that "the more the world isolates these countries, the harder it will be for them to control these outbreaks, the more cases there will be, and the less safe other countries will be. Like it or not, we’re connected."
The area currently experiencing outbreaks includes the countries of Guinea, Liberia, Sierra Leone, and Nigeria, with what Dr. Frieden said is a "dense, forested region that is the epicenter" located where the borders of all but Nigeria meet. The remote area is not serviced by radio or television and is rife with what Dr. Frieden called "misconceptions" about how the disease is transmitted.
"We can turn this around. Sometimes the problem can seem so large, it’s hard to get started, but we can chip away at the challenges, one by one," he said, inviting anyone with experience working in austere conditions, either as a health care provider or manager of an under-resourced facility, to consider volunteering his or her services, noting that the longer the crisis continues, the less stable the local communities will be.
In addition to nearly $20 million in aid from the U.S. Agency for International Development, for goods ranging from personal protection gear to resources for safer burials, the CDC will continue to support efforts by the World Health Organization (WHO) to contain the epidemic within the year, by deploying top CDC epidemic intelligence teams to help with tracking, treatment, and screening, he said.
The need for global coordination is not due to a lack of willingness from local officials and personnel to respond, according to Dr. Frieden.
"The countries are willing. In an Ebola treatment unit run by Doctors Without Borders, more than 90% of the staff are locals," Dr. Frieden said of one of the stops on his tour of West Africa. "Each of the presidents [of the affected countries] said the same thing to me: ‘Tell us what to do and we will do it. If we can’t do it, help us to do it. Teach us to care for Ebola patients and to manage the system more effectively.’ They need the world to work with them."
According to WHO, more than 1,400 patients have died of Ebola virus infection to date in this outbreak, making this the largest Ebola outbreak ever recorded. There are still "significant gaps in reporting in some intense transmission areas," and that the number of cases ultimately may top 20,000, according to WHO, which noted this outbreak has featured the infection and deaths of "an unprecedented number of health care workers."
There are no vaccines for Ebola approved by the Food and Drug Administration, although the National Institute of Allergy and Infectious Diseases currently is attempting to develop one.
As to treatments, ZMapp, a trio of monoclonal antibodies that was successfully used to treat two American health workers who were infected with Ebola, also has shown promise in a controlled trial with primates. According to ZMapp’s manufacturer, Mapp Biopharmaceuticals, the supply of the drug is currently exhausted and there is as yet no date for when more will be available.
On Twitter @whitneymcknight
Despite some signs of hope, the "window of opportunity" to contain and end the current Ebola virus outbreak in West Africa is shutting, causing the situation to worsen "significantly," according to officials at the Centers for Disease Control and Prevention.
"This is really the first epidemic of Ebola the world has ever known," Dr. Thomas Frieden, CDC director, said during a media briefing.
The prevailing belief, according to Dr. Frieden, is that the virus’s rapid spread is not due to mutation but instead to cultural and logistical obstacles.
"It’s not spreading in new ways, according to everything that we know," Dr. Frieden said. "It’s spreading through just two routes: people caring for other people ... and unsafe burial practices. ... That is really the Achilles’ heel. We know how it spreads; we know how to stop it. The challenge is to do that everywhere it is needed."
The Ebola virus is transmitted primarily through body fluids, but it also can be spread through contact with contaminated objects such as needles. Ebola is not spread through the air or by water.
Noting that rapid response is essential, and that data are lacking as to the actual numbers of those infected with the virus, Dr. Frieden outlined three key things that are needed to stem the epidemic: more resources; technical expertise in both health care management and logistics; and a coordinated global approach to ending the outbreak.
Dr. Frieden said it was a paradox that "the more the world isolates these countries, the harder it will be for them to control these outbreaks, the more cases there will be, and the less safe other countries will be. Like it or not, we’re connected."
The area currently experiencing outbreaks includes the countries of Guinea, Liberia, Sierra Leone, and Nigeria, with what Dr. Frieden said is a "dense, forested region that is the epicenter" located where the borders of all but Nigeria meet. The remote area is not serviced by radio or television and is rife with what Dr. Frieden called "misconceptions" about how the disease is transmitted.
"We can turn this around. Sometimes the problem can seem so large, it’s hard to get started, but we can chip away at the challenges, one by one," he said, inviting anyone with experience working in austere conditions, either as a health care provider or manager of an under-resourced facility, to consider volunteering his or her services, noting that the longer the crisis continues, the less stable the local communities will be.
In addition to nearly $20 million in aid from the U.S. Agency for International Development, for goods ranging from personal protection gear to resources for safer burials, the CDC will continue to support efforts by the World Health Organization (WHO) to contain the epidemic within the year, by deploying top CDC epidemic intelligence teams to help with tracking, treatment, and screening, he said.
The need for global coordination is not due to a lack of willingness from local officials and personnel to respond, according to Dr. Frieden.
"The countries are willing. In an Ebola treatment unit run by Doctors Without Borders, more than 90% of the staff are locals," Dr. Frieden said of one of the stops on his tour of West Africa. "Each of the presidents [of the affected countries] said the same thing to me: ‘Tell us what to do and we will do it. If we can’t do it, help us to do it. Teach us to care for Ebola patients and to manage the system more effectively.’ They need the world to work with them."
According to WHO, more than 1,400 patients have died of Ebola virus infection to date in this outbreak, making this the largest Ebola outbreak ever recorded. There are still "significant gaps in reporting in some intense transmission areas," and that the number of cases ultimately may top 20,000, according to WHO, which noted this outbreak has featured the infection and deaths of "an unprecedented number of health care workers."
There are no vaccines for Ebola approved by the Food and Drug Administration, although the National Institute of Allergy and Infectious Diseases currently is attempting to develop one.
As to treatments, ZMapp, a trio of monoclonal antibodies that was successfully used to treat two American health workers who were infected with Ebola, also has shown promise in a controlled trial with primates. According to ZMapp’s manufacturer, Mapp Biopharmaceuticals, the supply of the drug is currently exhausted and there is as yet no date for when more will be available.
On Twitter @whitneymcknight
FROM A CDC TELECONFERENCE
Severity of side effects key to choosing between lithium and quetiapine in bipolar I and II
HOLLYWOOD, FLA. – Because there is no clinically significant difference in bipolar spectrum symptom relief offered by either lithium or quetiapine, which mood stabilizer clinicians choose to prescribe should largely depend on what side effects patients can tolerate.
That’s the conclusion of a panel of experts who presented data from the Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder) clinical trial at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.
By randomly assigning the study’s 482 participating outpatient adults to either lithium or quetiapine, while allowing clinicians to prescribe adjunctive treatment as necessary; and by using a broader-than-usual set of inclusion criteria, the investigators hoped to provide clinicians with "real world" data on how the respective mood stabilizers perform.
"To my knowledge, this is the first randomized comparative effectiveness study of regular, expert care that looks at lithium versus quetiapine strategies of treatment, both with adjunctive personalized treatment when necessary," study coauthor Dr. Andrew A. Nierenberg told the audience in a well-attended session.
"We tortured the data to get a P value to pop out," said Dr. Nierenberg, who is the director of the Bipolar Clinic and Research Program at Massachusetts General Hospital in Boston. "The bottom line was that the treatment strategies, based on either lithium or quetiapine, were very similar. I think the clinical implication is that the choice of treatment really depends on someone’s tolerability. This may resurrect lithium as something [clinicians] should at least consider, because its use has gone down dramatically in the last 20 years or so."
Side effects such as metabolic or sleep disturbances were slightly less frequent in the lithium group, although the difference was not statistically significant; rates of suicidality and discontinuation of medication due to side effects were also similar across the two groups, according to Dr. David E. Kemp of the psychiatry department at Case Western Reserve University, Cleveland, and a study coauthor who also presented data during the session. Changes from baseline in mood stabilization were also virtually the same across the groups.
‘Rules of engagement’
The study enrolled adults aged 18-68 years who were at least mildly ill with either bipolar disorder I (68%) or II, with a Clinical Global Impression (CGI) score of at least 3, although the average CGI score was 4.5 (standard deviation of plus or minus 0.9). Of the 482 enrolled, 364 completed the study.
The so-called rules of engagement for clinicians from the 11 participating centers were that "they do everything they could to get their patients well," with the caveat that the lithium patient group not receive any antipsychotic, and the quetiapine patient group not receive lithium or any other antipsychotic.
"But they could get anything else that they needed," Dr. Nierenberg said.
At the time of enrollment, subjects were, in the estimation of their treating physician, experiencing symptoms that warranted a change in treatment, and that either lithium or quetiapine would be viable therapeutic options. Patients did not need to be lithium- or quetiapine-naive, but they could not have been treated with either drug in the previous 30 days. If they were already taking a second-generation antipsychotic, participants had to be willing to discontinue that medication and to be randomly assigned to either of the study drugs.
This strict adherence to one mood stabilizer, combined with adjunctive personalized treatments such as antidepressants or benzodiazepines, prescribed at the discretion of the treating clinician, ensured that the study tested the strategy of using either lithium or quetiapine as the base of treatment, Dr. Nierenberg said.
‘Similar’ results
Clinicians also were instructed to use the maximum tolerated dose of the respective mood stabilizer. For the 240 patients in the lithium group, the mean maximum tolerated dose was 1,007.5 mg, with the median dose being a "perfectly reasonable 900 mg," Dr. Nierenberg said. Blood lithium levels were taken at weeks 2, 16, and 24 and also were all found to be "reasonable," with most patients getting to at least 0.6 mEq/L by week 24.
For the 242 members of the quetiapine group, the maximum tolerated dose was 344.9 mg, with a median tolerated dose of 300 mg, which Dr. Nierenberg said was "what you would expect."
The overall result was that regardless of which mood stabilizer was prescribed along with adjunctive personalized treatment, the coprimary outcomes of the benefits and harms ratio from treatment effects over time (the CGI efficacy index), and the number of necessary clinical adjustments (changes in medication excluding titrations according to scale), were virtually parallel: For each primary outcome, the P value for the estimated change in baseline was less than .0001 for both lithium plus adjunctive treatment, and quetiapine plus adjunctive treatment.
Further, Dr. Nierenberg reported the "unexpected" result that at 6 months, about a quarter of each group was observed to be doing well without any adjunctive personalized treatments (23.8% of the lithium group; 27.3% of the quetiapine group; P = .14). "We thought that everybody would be on multiple things," Dr. Nierenberg said.
There was also no real difference in the time to discontinuation. "We were actually surprised that at 6 months, about three-quarters of the patients were still on the study drug, which was pretty good considering that this was a very ill population," Dr. Nierenberg said.
Using a CGI bipolar severity scale rating of up to 2, maintained for at least 8 weeks, the investigators found that overall, 20% were considered doing "really well"; it was also about 20% for the lithium plus adjunctive therapy group and the quetiapine and adjunctive therapy group (P = .14 for all three).
Because the Agency for Healthcare Research and Quality–funded study mandated that researchers end their investigation at precisely 36 months, Dr. Nierenberg said the study sites "randomized the 482 patients to 6 months of treatment within 36 months from start to finish," but he added that the investigators would have preferred to conduct a full 2-year study of participants.
"The good news was that most of the patients actually did improve substantially; the bad news is that while maybe a quarter did really well by the end of 6 months, we don’t know whether if we were to extend the study out further, we would see a difference between the two groups, whether they would continue to improve, or whether they would relapse," he said.
Adverse effects, predictors of response
Because study participants were followed for only 6 months, the long-term adverse effects of many years of exposure to either mood stabilizer, such as renal impairment with lithium or type II diabetes with quetiapine, were not considered, Dr. Kemp said. The adverse-effect profile for lithium generally includes a narrow therapeutic index; nausea, vomiting, and diarrhea; renal impairment; and hypothyroidism. Although Dr. Kemp said that the long-term adverse effects of quetiapine are understudied, known short-term side effects include the potential for sedation or somnolence, and weight gain.
Changes in baseline on the Frequency and Intensity of Side Effects Ratings for the quetiapine plus adjunctive personalized treatment arm were slightly more adverse than for the lithium and additional treatment arm. For the lithium plus adjunctive treatment group, the mean frequency of side effects was –1.41 (–1.78, –1.04 SD); the mean intensity of side effects was –1.48 (–1.80, –1.15 SD); and the mean level of impairment was –1.13 (–1.43, –0.82 SD). For the quetiapine and adjunctive treatment group, the mean frequency measure was –1.08 (–1.45, –0.72 SD); the intensity was –1.12 (–1.44, –0.79 SD); and the impairment was –0.77 (–1.07, –0.47 SD). For all scores in both groups, P was less than .001.
The changes from baseline on the Bipolar Index Severity Scale (BISS) overall for the quetiapine plus adjunctive treatment group was –28.56 (–10.91, –26.21 SD; P less than .0001). For the lithium plus adjunctive treatment group, it was –27.61 (–29.99, –25.24 SD; P less than .0001). The overall difference between the two groups was 0.94 (–2.10, 3.99 SD; P = .54).
Scores on the Longitudinal Interval Follow-up Evaluation Range of Impaired Functioning Tool also slightly favored lithium: –3.74 (–4.29, –3.19 SD) vs. –3.6 (–4.15, –3.07 SD) for quetiapine (P less than .0001 for all).
To the investigators’ surprise, among those with comorbid anxiety, the lithium plus adjunctive treatment group had fewer necessary clinical adjustments per month than did the quetiapine plus adjunctive treatment group, according to Dr. Nierenberg: –0.83 vs. 1.11 (P = .02).
"That seemed counterintuitive, and this difference was only with anxiety, not with any other comorbid psychiatric conditions," Dr. Nierenberg said. He hypothesized that it was possible benzodiazepines were used more frequently and easily with lithium than with quetiapine, but said future analyses would give a clearer answer. "We have a detailed database of every other medication used: when it was started, when it was stopped, and the reason why everything was done."
Not having current anxiety disorder was predictive of a better outcome (odds ratio, 1.81; P = .02), as was employment (OR, 1.67; P = .04). Those with bipolar II disorder responded better to treatment than those with bipolar disorder I, having an OR of response to treatment of nearly 1.8 P = .03). "That was a surprise to us, too," Dr. Nierenberg said.
Just over a quarter (27%) of the study population had metabolic syndrome, according to Dr. Kemp, who said this was not found to influence treatment outcomes.
Nearly half of the overall population was obese (48%), and slightly less than half (44%) had adipose. Prospective analysis indicated that patients with either obesity or adiposity tended to show less improvement in their CGI scores in a statistically significant way, regardless of which mood stabilizer they were on.
"Part of that might be due to overlapping pathophysiology between bipolar disorder and obesity," Dr. Kemp said. "Much of that is centered around inflammation in the central nervous system, as well as alterations in adipokines receptor levels and mitochondrial dysfunction."
"A key issue is to take care of obesity," said panel discussant Dr. Mauricio Tohen, chairman of psychiatry at the University of New Mexico in Albuquerque. "Regardless of the treatment, when there is obesity, the outcome will not be as good."
Efficacy vs. ‘generalizability’
Adjunctive personalized treatment was measured to help minimize the lack of assay sensitivity and internal validity typically inherent in comparative effectiveness trials, while also achieving more broadly applicable results.
"The right study depends on the right question," Dr. Tohen said. "If the question is whether a particular treatment has efficacy and is safe, then of course, we need an efficacy study. The problem with efficacy studies is that they limit the generalizability."
Instead, Dr. Tohen, who disclosed he spent more than a decade evaluating efficacy studies for both Eli Lily and AstraZeneca (makers of quetiapine), praised the metric of the adjunctive personalized treatments, and said a study should answer the question, "Of all the patients in my clinic, who will do better on which treatment? With efficacy studies you cannot answer that question because of the exclusion criteria that need to be taken into account."
In addition, Dr. Tohen said the metric likely would increase in importance under the Affordable Care Act, where efficacy is not the only consideration. "For example, if a patient relapses earlier, it might not be reimbursed, so asking what other outcomes we need to measure in [these kinds of] comparative effectiveness studies is very important."
In the CHOICE study, which had no placebo group, participating physicians were asked to track each patient’s dosage changes, missed doses, new medications added, discontinued medications, and the specific reasons for any of these changes. Changes that were made because of lack of effectiveness or intolerance were measured; however, planned dosage titrations according to normal scales were not considered necessary clinical adjustments but simply the regular course of treatment.
This heterogeneity of adjunctive treatment was seen by the investigators as a way to reflect "real world" practice, although they also noted it could be seen as a limitation to the study.
Another way the study was designed to reflect real-world practice was the inclusion of a broader-than-usual group of participants, and asking them for their feedback at the end of the study period.
"Before we put together these data, we held a stakeholder summit," Dr. Nierenberg said. "We invited patients and their advocates to help us interpret the study. They felt strongly that this was a reasonably positive study, because they thought that people really did get better. You could report these data toward the negative or the positive, but we reported toward the positive because that is what the stakeholders asked us to do." Dr. Tohen said that this kind of feedback in a comparative effectiveness study was another way these kinds of studies could help guide practice in the era of the Affordable Care Act.
As for who was actually admitted to the study, "exclusions were minimal," said Dr. Edward S. Friedman of the psychiatry department at the University of Pittsburgh. Those with a history of drug or alcohol dependence in the previous 30 days, a demonstrated intolerance to either study drug, or severe cardiovascular or renal disease were excluded, as were those with unstable thyroid disease, and pregnant or breastfeeding women.
Overall, the group was multiethnic, although nearly three-quarters were white and 20% were black. Roughly a third of the entire study population was employed, a third unemployed, and the rest were students, retirees, or those on disability.
The overall BISS score at enrollment averaged 56.1 (SD plus or minus 18.8). The average BISS depression score was 37.6 (SD plus or minus 14.0), and the average BISS mania score was 18.5 (SD plus or minus 12.1).
There were many comorbid psychiatric conditions, ranging from panic disorder to agoraphobia, although substance use was highest (61.4%). Current anxiety disorder also was prevalent at 58%.
"The CHOICE sample was similar in age and gender to previous efficacy studies," Dr. Friedman said. "It was more representative of the U.S. population than efficacy studies such as STEP-BD or LITMUS."
The 283 women (59% of the study) were more likely to report having spent a greater percentage of time depressed in the previous year, although the percentage of time spent in manic or hypomanic states was equal across both genders.
"This study was composed of sick individuals who had been sick for a considerable period of time," Dr. Friedman said.
For example, in the CHOICE study, 47% had been hospitalized for their bipolar disorder previously, vs. 43% in the LITMUS study. CHOICE participants had an attempted suicide rate of 36%, which fell between the 41% in the LITMUS trial and the 33.3% in an efficacy study conducted by Dr. Joseph R. Calabrese and his colleagues (J. Clin. Psychiatry 1999;60:79-88).
The average age for the first depressive episode for CHOICE participants was 16.4 years; the first manic episode tended to be at 20 years; and the first mood episode tended to be around 15.5 years. These data were similar to those in the LITMUS study, but differed from data in several efficacy studies such as the one by Dr. Calabrese, where the average age was 31.3 years.
"You might anticipate that in these specialty clinics we would have very few medication-naive patients, and yet we did," Dr. Friedman said during a postpanel audience participation session. "Looking for patients with a low threshold, we brought in patients who were very sick. They were also older, with lots of previous episodes. Maybe we missed younger patients who didn’t have as many previous episodes."
"These are the patients you would see in your practice," Dr. Nierenberg said before asking the audience what they think should be studied next in a comparative effectiveness trial. "We could look at the use of different antipsychotics, the combinations we use, with or without lamotrigine," he said.
"Most of the decisions that are made in medicine are made without evidence. Most of the things that are done are done without evidence. You have combinations that were never studied before or never even used before, and it’s across all medicine." Because medicine needs to be learning more, he said the audience needed to participate. "What are the questions that need to be asked?"
On Twitter @whitneymcknight
HOLLYWOOD, FLA. – Because there is no clinically significant difference in bipolar spectrum symptom relief offered by either lithium or quetiapine, which mood stabilizer clinicians choose to prescribe should largely depend on what side effects patients can tolerate.
That’s the conclusion of a panel of experts who presented data from the Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder) clinical trial at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.
By randomly assigning the study’s 482 participating outpatient adults to either lithium or quetiapine, while allowing clinicians to prescribe adjunctive treatment as necessary; and by using a broader-than-usual set of inclusion criteria, the investigators hoped to provide clinicians with "real world" data on how the respective mood stabilizers perform.
"To my knowledge, this is the first randomized comparative effectiveness study of regular, expert care that looks at lithium versus quetiapine strategies of treatment, both with adjunctive personalized treatment when necessary," study coauthor Dr. Andrew A. Nierenberg told the audience in a well-attended session.
"We tortured the data to get a P value to pop out," said Dr. Nierenberg, who is the director of the Bipolar Clinic and Research Program at Massachusetts General Hospital in Boston. "The bottom line was that the treatment strategies, based on either lithium or quetiapine, were very similar. I think the clinical implication is that the choice of treatment really depends on someone’s tolerability. This may resurrect lithium as something [clinicians] should at least consider, because its use has gone down dramatically in the last 20 years or so."
Side effects such as metabolic or sleep disturbances were slightly less frequent in the lithium group, although the difference was not statistically significant; rates of suicidality and discontinuation of medication due to side effects were also similar across the two groups, according to Dr. David E. Kemp of the psychiatry department at Case Western Reserve University, Cleveland, and a study coauthor who also presented data during the session. Changes from baseline in mood stabilization were also virtually the same across the groups.
‘Rules of engagement’
The study enrolled adults aged 18-68 years who were at least mildly ill with either bipolar disorder I (68%) or II, with a Clinical Global Impression (CGI) score of at least 3, although the average CGI score was 4.5 (standard deviation of plus or minus 0.9). Of the 482 enrolled, 364 completed the study.
The so-called rules of engagement for clinicians from the 11 participating centers were that "they do everything they could to get their patients well," with the caveat that the lithium patient group not receive any antipsychotic, and the quetiapine patient group not receive lithium or any other antipsychotic.
"But they could get anything else that they needed," Dr. Nierenberg said.
At the time of enrollment, subjects were, in the estimation of their treating physician, experiencing symptoms that warranted a change in treatment, and that either lithium or quetiapine would be viable therapeutic options. Patients did not need to be lithium- or quetiapine-naive, but they could not have been treated with either drug in the previous 30 days. If they were already taking a second-generation antipsychotic, participants had to be willing to discontinue that medication and to be randomly assigned to either of the study drugs.
This strict adherence to one mood stabilizer, combined with adjunctive personalized treatments such as antidepressants or benzodiazepines, prescribed at the discretion of the treating clinician, ensured that the study tested the strategy of using either lithium or quetiapine as the base of treatment, Dr. Nierenberg said.
‘Similar’ results
Clinicians also were instructed to use the maximum tolerated dose of the respective mood stabilizer. For the 240 patients in the lithium group, the mean maximum tolerated dose was 1,007.5 mg, with the median dose being a "perfectly reasonable 900 mg," Dr. Nierenberg said. Blood lithium levels were taken at weeks 2, 16, and 24 and also were all found to be "reasonable," with most patients getting to at least 0.6 mEq/L by week 24.
For the 242 members of the quetiapine group, the maximum tolerated dose was 344.9 mg, with a median tolerated dose of 300 mg, which Dr. Nierenberg said was "what you would expect."
The overall result was that regardless of which mood stabilizer was prescribed along with adjunctive personalized treatment, the coprimary outcomes of the benefits and harms ratio from treatment effects over time (the CGI efficacy index), and the number of necessary clinical adjustments (changes in medication excluding titrations according to scale), were virtually parallel: For each primary outcome, the P value for the estimated change in baseline was less than .0001 for both lithium plus adjunctive treatment, and quetiapine plus adjunctive treatment.
Further, Dr. Nierenberg reported the "unexpected" result that at 6 months, about a quarter of each group was observed to be doing well without any adjunctive personalized treatments (23.8% of the lithium group; 27.3% of the quetiapine group; P = .14). "We thought that everybody would be on multiple things," Dr. Nierenberg said.
There was also no real difference in the time to discontinuation. "We were actually surprised that at 6 months, about three-quarters of the patients were still on the study drug, which was pretty good considering that this was a very ill population," Dr. Nierenberg said.
Using a CGI bipolar severity scale rating of up to 2, maintained for at least 8 weeks, the investigators found that overall, 20% were considered doing "really well"; it was also about 20% for the lithium plus adjunctive therapy group and the quetiapine and adjunctive therapy group (P = .14 for all three).
Because the Agency for Healthcare Research and Quality–funded study mandated that researchers end their investigation at precisely 36 months, Dr. Nierenberg said the study sites "randomized the 482 patients to 6 months of treatment within 36 months from start to finish," but he added that the investigators would have preferred to conduct a full 2-year study of participants.
"The good news was that most of the patients actually did improve substantially; the bad news is that while maybe a quarter did really well by the end of 6 months, we don’t know whether if we were to extend the study out further, we would see a difference between the two groups, whether they would continue to improve, or whether they would relapse," he said.
Adverse effects, predictors of response
Because study participants were followed for only 6 months, the long-term adverse effects of many years of exposure to either mood stabilizer, such as renal impairment with lithium or type II diabetes with quetiapine, were not considered, Dr. Kemp said. The adverse-effect profile for lithium generally includes a narrow therapeutic index; nausea, vomiting, and diarrhea; renal impairment; and hypothyroidism. Although Dr. Kemp said that the long-term adverse effects of quetiapine are understudied, known short-term side effects include the potential for sedation or somnolence, and weight gain.
Changes in baseline on the Frequency and Intensity of Side Effects Ratings for the quetiapine plus adjunctive personalized treatment arm were slightly more adverse than for the lithium and additional treatment arm. For the lithium plus adjunctive treatment group, the mean frequency of side effects was –1.41 (–1.78, –1.04 SD); the mean intensity of side effects was –1.48 (–1.80, –1.15 SD); and the mean level of impairment was –1.13 (–1.43, –0.82 SD). For the quetiapine and adjunctive treatment group, the mean frequency measure was –1.08 (–1.45, –0.72 SD); the intensity was –1.12 (–1.44, –0.79 SD); and the impairment was –0.77 (–1.07, –0.47 SD). For all scores in both groups, P was less than .001.
The changes from baseline on the Bipolar Index Severity Scale (BISS) overall for the quetiapine plus adjunctive treatment group was –28.56 (–10.91, –26.21 SD; P less than .0001). For the lithium plus adjunctive treatment group, it was –27.61 (–29.99, –25.24 SD; P less than .0001). The overall difference between the two groups was 0.94 (–2.10, 3.99 SD; P = .54).
Scores on the Longitudinal Interval Follow-up Evaluation Range of Impaired Functioning Tool also slightly favored lithium: –3.74 (–4.29, –3.19 SD) vs. –3.6 (–4.15, –3.07 SD) for quetiapine (P less than .0001 for all).
To the investigators’ surprise, among those with comorbid anxiety, the lithium plus adjunctive treatment group had fewer necessary clinical adjustments per month than did the quetiapine plus adjunctive treatment group, according to Dr. Nierenberg: –0.83 vs. 1.11 (P = .02).
"That seemed counterintuitive, and this difference was only with anxiety, not with any other comorbid psychiatric conditions," Dr. Nierenberg said. He hypothesized that it was possible benzodiazepines were used more frequently and easily with lithium than with quetiapine, but said future analyses would give a clearer answer. "We have a detailed database of every other medication used: when it was started, when it was stopped, and the reason why everything was done."
Not having current anxiety disorder was predictive of a better outcome (odds ratio, 1.81; P = .02), as was employment (OR, 1.67; P = .04). Those with bipolar II disorder responded better to treatment than those with bipolar disorder I, having an OR of response to treatment of nearly 1.8 P = .03). "That was a surprise to us, too," Dr. Nierenberg said.
Just over a quarter (27%) of the study population had metabolic syndrome, according to Dr. Kemp, who said this was not found to influence treatment outcomes.
Nearly half of the overall population was obese (48%), and slightly less than half (44%) had adipose. Prospective analysis indicated that patients with either obesity or adiposity tended to show less improvement in their CGI scores in a statistically significant way, regardless of which mood stabilizer they were on.
"Part of that might be due to overlapping pathophysiology between bipolar disorder and obesity," Dr. Kemp said. "Much of that is centered around inflammation in the central nervous system, as well as alterations in adipokines receptor levels and mitochondrial dysfunction."
"A key issue is to take care of obesity," said panel discussant Dr. Mauricio Tohen, chairman of psychiatry at the University of New Mexico in Albuquerque. "Regardless of the treatment, when there is obesity, the outcome will not be as good."
Efficacy vs. ‘generalizability’
Adjunctive personalized treatment was measured to help minimize the lack of assay sensitivity and internal validity typically inherent in comparative effectiveness trials, while also achieving more broadly applicable results.
"The right study depends on the right question," Dr. Tohen said. "If the question is whether a particular treatment has efficacy and is safe, then of course, we need an efficacy study. The problem with efficacy studies is that they limit the generalizability."
Instead, Dr. Tohen, who disclosed he spent more than a decade evaluating efficacy studies for both Eli Lily and AstraZeneca (makers of quetiapine), praised the metric of the adjunctive personalized treatments, and said a study should answer the question, "Of all the patients in my clinic, who will do better on which treatment? With efficacy studies you cannot answer that question because of the exclusion criteria that need to be taken into account."
In addition, Dr. Tohen said the metric likely would increase in importance under the Affordable Care Act, where efficacy is not the only consideration. "For example, if a patient relapses earlier, it might not be reimbursed, so asking what other outcomes we need to measure in [these kinds of] comparative effectiveness studies is very important."
In the CHOICE study, which had no placebo group, participating physicians were asked to track each patient’s dosage changes, missed doses, new medications added, discontinued medications, and the specific reasons for any of these changes. Changes that were made because of lack of effectiveness or intolerance were measured; however, planned dosage titrations according to normal scales were not considered necessary clinical adjustments but simply the regular course of treatment.
This heterogeneity of adjunctive treatment was seen by the investigators as a way to reflect "real world" practice, although they also noted it could be seen as a limitation to the study.
Another way the study was designed to reflect real-world practice was the inclusion of a broader-than-usual group of participants, and asking them for their feedback at the end of the study period.
"Before we put together these data, we held a stakeholder summit," Dr. Nierenberg said. "We invited patients and their advocates to help us interpret the study. They felt strongly that this was a reasonably positive study, because they thought that people really did get better. You could report these data toward the negative or the positive, but we reported toward the positive because that is what the stakeholders asked us to do." Dr. Tohen said that this kind of feedback in a comparative effectiveness study was another way these kinds of studies could help guide practice in the era of the Affordable Care Act.
As for who was actually admitted to the study, "exclusions were minimal," said Dr. Edward S. Friedman of the psychiatry department at the University of Pittsburgh. Those with a history of drug or alcohol dependence in the previous 30 days, a demonstrated intolerance to either study drug, or severe cardiovascular or renal disease were excluded, as were those with unstable thyroid disease, and pregnant or breastfeeding women.
Overall, the group was multiethnic, although nearly three-quarters were white and 20% were black. Roughly a third of the entire study population was employed, a third unemployed, and the rest were students, retirees, or those on disability.
The overall BISS score at enrollment averaged 56.1 (SD plus or minus 18.8). The average BISS depression score was 37.6 (SD plus or minus 14.0), and the average BISS mania score was 18.5 (SD plus or minus 12.1).
There were many comorbid psychiatric conditions, ranging from panic disorder to agoraphobia, although substance use was highest (61.4%). Current anxiety disorder also was prevalent at 58%.
"The CHOICE sample was similar in age and gender to previous efficacy studies," Dr. Friedman said. "It was more representative of the U.S. population than efficacy studies such as STEP-BD or LITMUS."
The 283 women (59% of the study) were more likely to report having spent a greater percentage of time depressed in the previous year, although the percentage of time spent in manic or hypomanic states was equal across both genders.
"This study was composed of sick individuals who had been sick for a considerable period of time," Dr. Friedman said.
For example, in the CHOICE study, 47% had been hospitalized for their bipolar disorder previously, vs. 43% in the LITMUS study. CHOICE participants had an attempted suicide rate of 36%, which fell between the 41% in the LITMUS trial and the 33.3% in an efficacy study conducted by Dr. Joseph R. Calabrese and his colleagues (J. Clin. Psychiatry 1999;60:79-88).
The average age for the first depressive episode for CHOICE participants was 16.4 years; the first manic episode tended to be at 20 years; and the first mood episode tended to be around 15.5 years. These data were similar to those in the LITMUS study, but differed from data in several efficacy studies such as the one by Dr. Calabrese, where the average age was 31.3 years.
"You might anticipate that in these specialty clinics we would have very few medication-naive patients, and yet we did," Dr. Friedman said during a postpanel audience participation session. "Looking for patients with a low threshold, we brought in patients who were very sick. They were also older, with lots of previous episodes. Maybe we missed younger patients who didn’t have as many previous episodes."
"These are the patients you would see in your practice," Dr. Nierenberg said before asking the audience what they think should be studied next in a comparative effectiveness trial. "We could look at the use of different antipsychotics, the combinations we use, with or without lamotrigine," he said.
"Most of the decisions that are made in medicine are made without evidence. Most of the things that are done are done without evidence. You have combinations that were never studied before or never even used before, and it’s across all medicine." Because medicine needs to be learning more, he said the audience needed to participate. "What are the questions that need to be asked?"
On Twitter @whitneymcknight
HOLLYWOOD, FLA. – Because there is no clinically significant difference in bipolar spectrum symptom relief offered by either lithium or quetiapine, which mood stabilizer clinicians choose to prescribe should largely depend on what side effects patients can tolerate.
That’s the conclusion of a panel of experts who presented data from the Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder) clinical trial at a meeting of the American Society of Clinical Psychopharmacology, formerly known as the New Clinical Drug Evaluation Unit meeting.
By randomly assigning the study’s 482 participating outpatient adults to either lithium or quetiapine, while allowing clinicians to prescribe adjunctive treatment as necessary; and by using a broader-than-usual set of inclusion criteria, the investigators hoped to provide clinicians with "real world" data on how the respective mood stabilizers perform.
"To my knowledge, this is the first randomized comparative effectiveness study of regular, expert care that looks at lithium versus quetiapine strategies of treatment, both with adjunctive personalized treatment when necessary," study coauthor Dr. Andrew A. Nierenberg told the audience in a well-attended session.
"We tortured the data to get a P value to pop out," said Dr. Nierenberg, who is the director of the Bipolar Clinic and Research Program at Massachusetts General Hospital in Boston. "The bottom line was that the treatment strategies, based on either lithium or quetiapine, were very similar. I think the clinical implication is that the choice of treatment really depends on someone’s tolerability. This may resurrect lithium as something [clinicians] should at least consider, because its use has gone down dramatically in the last 20 years or so."
Side effects such as metabolic or sleep disturbances were slightly less frequent in the lithium group, although the difference was not statistically significant; rates of suicidality and discontinuation of medication due to side effects were also similar across the two groups, according to Dr. David E. Kemp of the psychiatry department at Case Western Reserve University, Cleveland, and a study coauthor who also presented data during the session. Changes from baseline in mood stabilization were also virtually the same across the groups.
‘Rules of engagement’
The study enrolled adults aged 18-68 years who were at least mildly ill with either bipolar disorder I (68%) or II, with a Clinical Global Impression (CGI) score of at least 3, although the average CGI score was 4.5 (standard deviation of plus or minus 0.9). Of the 482 enrolled, 364 completed the study.
The so-called rules of engagement for clinicians from the 11 participating centers were that "they do everything they could to get their patients well," with the caveat that the lithium patient group not receive any antipsychotic, and the quetiapine patient group not receive lithium or any other antipsychotic.
"But they could get anything else that they needed," Dr. Nierenberg said.
At the time of enrollment, subjects were, in the estimation of their treating physician, experiencing symptoms that warranted a change in treatment, and that either lithium or quetiapine would be viable therapeutic options. Patients did not need to be lithium- or quetiapine-naive, but they could not have been treated with either drug in the previous 30 days. If they were already taking a second-generation antipsychotic, participants had to be willing to discontinue that medication and to be randomly assigned to either of the study drugs.
This strict adherence to one mood stabilizer, combined with adjunctive personalized treatments such as antidepressants or benzodiazepines, prescribed at the discretion of the treating clinician, ensured that the study tested the strategy of using either lithium or quetiapine as the base of treatment, Dr. Nierenberg said.
‘Similar’ results
Clinicians also were instructed to use the maximum tolerated dose of the respective mood stabilizer. For the 240 patients in the lithium group, the mean maximum tolerated dose was 1,007.5 mg, with the median dose being a "perfectly reasonable 900 mg," Dr. Nierenberg said. Blood lithium levels were taken at weeks 2, 16, and 24 and also were all found to be "reasonable," with most patients getting to at least 0.6 mEq/L by week 24.
For the 242 members of the quetiapine group, the maximum tolerated dose was 344.9 mg, with a median tolerated dose of 300 mg, which Dr. Nierenberg said was "what you would expect."
The overall result was that regardless of which mood stabilizer was prescribed along with adjunctive personalized treatment, the coprimary outcomes of the benefits and harms ratio from treatment effects over time (the CGI efficacy index), and the number of necessary clinical adjustments (changes in medication excluding titrations according to scale), were virtually parallel: For each primary outcome, the P value for the estimated change in baseline was less than .0001 for both lithium plus adjunctive treatment, and quetiapine plus adjunctive treatment.
Further, Dr. Nierenberg reported the "unexpected" result that at 6 months, about a quarter of each group was observed to be doing well without any adjunctive personalized treatments (23.8% of the lithium group; 27.3% of the quetiapine group; P = .14). "We thought that everybody would be on multiple things," Dr. Nierenberg said.
There was also no real difference in the time to discontinuation. "We were actually surprised that at 6 months, about three-quarters of the patients were still on the study drug, which was pretty good considering that this was a very ill population," Dr. Nierenberg said.
Using a CGI bipolar severity scale rating of up to 2, maintained for at least 8 weeks, the investigators found that overall, 20% were considered doing "really well"; it was also about 20% for the lithium plus adjunctive therapy group and the quetiapine and adjunctive therapy group (P = .14 for all three).
Because the Agency for Healthcare Research and Quality–funded study mandated that researchers end their investigation at precisely 36 months, Dr. Nierenberg said the study sites "randomized the 482 patients to 6 months of treatment within 36 months from start to finish," but he added that the investigators would have preferred to conduct a full 2-year study of participants.
"The good news was that most of the patients actually did improve substantially; the bad news is that while maybe a quarter did really well by the end of 6 months, we don’t know whether if we were to extend the study out further, we would see a difference between the two groups, whether they would continue to improve, or whether they would relapse," he said.
Adverse effects, predictors of response
Because study participants were followed for only 6 months, the long-term adverse effects of many years of exposure to either mood stabilizer, such as renal impairment with lithium or type II diabetes with quetiapine, were not considered, Dr. Kemp said. The adverse-effect profile for lithium generally includes a narrow therapeutic index; nausea, vomiting, and diarrhea; renal impairment; and hypothyroidism. Although Dr. Kemp said that the long-term adverse effects of quetiapine are understudied, known short-term side effects include the potential for sedation or somnolence, and weight gain.
Changes in baseline on the Frequency and Intensity of Side Effects Ratings for the quetiapine plus adjunctive personalized treatment arm were slightly more adverse than for the lithium and additional treatment arm. For the lithium plus adjunctive treatment group, the mean frequency of side effects was –1.41 (–1.78, –1.04 SD); the mean intensity of side effects was –1.48 (–1.80, –1.15 SD); and the mean level of impairment was –1.13 (–1.43, –0.82 SD). For the quetiapine and adjunctive treatment group, the mean frequency measure was –1.08 (–1.45, –0.72 SD); the intensity was –1.12 (–1.44, –0.79 SD); and the impairment was –0.77 (–1.07, –0.47 SD). For all scores in both groups, P was less than .001.
The changes from baseline on the Bipolar Index Severity Scale (BISS) overall for the quetiapine plus adjunctive treatment group was –28.56 (–10.91, –26.21 SD; P less than .0001). For the lithium plus adjunctive treatment group, it was –27.61 (–29.99, –25.24 SD; P less than .0001). The overall difference between the two groups was 0.94 (–2.10, 3.99 SD; P = .54).
Scores on the Longitudinal Interval Follow-up Evaluation Range of Impaired Functioning Tool also slightly favored lithium: –3.74 (–4.29, –3.19 SD) vs. –3.6 (–4.15, –3.07 SD) for quetiapine (P less than .0001 for all).
To the investigators’ surprise, among those with comorbid anxiety, the lithium plus adjunctive treatment group had fewer necessary clinical adjustments per month than did the quetiapine plus adjunctive treatment group, according to Dr. Nierenberg: –0.83 vs. 1.11 (P = .02).
"That seemed counterintuitive, and this difference was only with anxiety, not with any other comorbid psychiatric conditions," Dr. Nierenberg said. He hypothesized that it was possible benzodiazepines were used more frequently and easily with lithium than with quetiapine, but said future analyses would give a clearer answer. "We have a detailed database of every other medication used: when it was started, when it was stopped, and the reason why everything was done."
Not having current anxiety disorder was predictive of a better outcome (odds ratio, 1.81; P = .02), as was employment (OR, 1.67; P = .04). Those with bipolar II disorder responded better to treatment than those with bipolar disorder I, having an OR of response to treatment of nearly 1.8 P = .03). "That was a surprise to us, too," Dr. Nierenberg said.
Just over a quarter (27%) of the study population had metabolic syndrome, according to Dr. Kemp, who said this was not found to influence treatment outcomes.
Nearly half of the overall population was obese (48%), and slightly less than half (44%) had adipose. Prospective analysis indicated that patients with either obesity or adiposity tended to show less improvement in their CGI scores in a statistically significant way, regardless of which mood stabilizer they were on.
"Part of that might be due to overlapping pathophysiology between bipolar disorder and obesity," Dr. Kemp said. "Much of that is centered around inflammation in the central nervous system, as well as alterations in adipokines receptor levels and mitochondrial dysfunction."
"A key issue is to take care of obesity," said panel discussant Dr. Mauricio Tohen, chairman of psychiatry at the University of New Mexico in Albuquerque. "Regardless of the treatment, when there is obesity, the outcome will not be as good."
Efficacy vs. ‘generalizability’
Adjunctive personalized treatment was measured to help minimize the lack of assay sensitivity and internal validity typically inherent in comparative effectiveness trials, while also achieving more broadly applicable results.
"The right study depends on the right question," Dr. Tohen said. "If the question is whether a particular treatment has efficacy and is safe, then of course, we need an efficacy study. The problem with efficacy studies is that they limit the generalizability."
Instead, Dr. Tohen, who disclosed he spent more than a decade evaluating efficacy studies for both Eli Lily and AstraZeneca (makers of quetiapine), praised the metric of the adjunctive personalized treatments, and said a study should answer the question, "Of all the patients in my clinic, who will do better on which treatment? With efficacy studies you cannot answer that question because of the exclusion criteria that need to be taken into account."
In addition, Dr. Tohen said the metric likely would increase in importance under the Affordable Care Act, where efficacy is not the only consideration. "For example, if a patient relapses earlier, it might not be reimbursed, so asking what other outcomes we need to measure in [these kinds of] comparative effectiveness studies is very important."
In the CHOICE study, which had no placebo group, participating physicians were asked to track each patient’s dosage changes, missed doses, new medications added, discontinued medications, and the specific reasons for any of these changes. Changes that were made because of lack of effectiveness or intolerance were measured; however, planned dosage titrations according to normal scales were not considered necessary clinical adjustments but simply the regular course of treatment.
This heterogeneity of adjunctive treatment was seen by the investigators as a way to reflect "real world" practice, although they also noted it could be seen as a limitation to the study.
Another way the study was designed to reflect real-world practice was the inclusion of a broader-than-usual group of participants, and asking them for their feedback at the end of the study period.
"Before we put together these data, we held a stakeholder summit," Dr. Nierenberg said. "We invited patients and their advocates to help us interpret the study. They felt strongly that this was a reasonably positive study, because they thought that people really did get better. You could report these data toward the negative or the positive, but we reported toward the positive because that is what the stakeholders asked us to do." Dr. Tohen said that this kind of feedback in a comparative effectiveness study was another way these kinds of studies could help guide practice in the era of the Affordable Care Act.
As for who was actually admitted to the study, "exclusions were minimal," said Dr. Edward S. Friedman of the psychiatry department at the University of Pittsburgh. Those with a history of drug or alcohol dependence in the previous 30 days, a demonstrated intolerance to either study drug, or severe cardiovascular or renal disease were excluded, as were those with unstable thyroid disease, and pregnant or breastfeeding women.
Overall, the group was multiethnic, although nearly three-quarters were white and 20% were black. Roughly a third of the entire study population was employed, a third unemployed, and the rest were students, retirees, or those on disability.
The overall BISS score at enrollment averaged 56.1 (SD plus or minus 18.8). The average BISS depression score was 37.6 (SD plus or minus 14.0), and the average BISS mania score was 18.5 (SD plus or minus 12.1).
There were many comorbid psychiatric conditions, ranging from panic disorder to agoraphobia, although substance use was highest (61.4%). Current anxiety disorder also was prevalent at 58%.
"The CHOICE sample was similar in age and gender to previous efficacy studies," Dr. Friedman said. "It was more representative of the U.S. population than efficacy studies such as STEP-BD or LITMUS."
The 283 women (59% of the study) were more likely to report having spent a greater percentage of time depressed in the previous year, although the percentage of time spent in manic or hypomanic states was equal across both genders.
"This study was composed of sick individuals who had been sick for a considerable period of time," Dr. Friedman said.
For example, in the CHOICE study, 47% had been hospitalized for their bipolar disorder previously, vs. 43% in the LITMUS study. CHOICE participants had an attempted suicide rate of 36%, which fell between the 41% in the LITMUS trial and the 33.3% in an efficacy study conducted by Dr. Joseph R. Calabrese and his colleagues (J. Clin. Psychiatry 1999;60:79-88).
The average age for the first depressive episode for CHOICE participants was 16.4 years; the first manic episode tended to be at 20 years; and the first mood episode tended to be around 15.5 years. These data were similar to those in the LITMUS study, but differed from data in several efficacy studies such as the one by Dr. Calabrese, where the average age was 31.3 years.
"You might anticipate that in these specialty clinics we would have very few medication-naive patients, and yet we did," Dr. Friedman said during a postpanel audience participation session. "Looking for patients with a low threshold, we brought in patients who were very sick. They were also older, with lots of previous episodes. Maybe we missed younger patients who didn’t have as many previous episodes."
"These are the patients you would see in your practice," Dr. Nierenberg said before asking the audience what they think should be studied next in a comparative effectiveness trial. "We could look at the use of different antipsychotics, the combinations we use, with or without lamotrigine," he said.
"Most of the decisions that are made in medicine are made without evidence. Most of the things that are done are done without evidence. You have combinations that were never studied before or never even used before, and it’s across all medicine." Because medicine needs to be learning more, he said the audience needed to participate. "What are the questions that need to be asked?"
On Twitter @whitneymcknight
AT THE ASCP ANNUAL MEETING
Key clinical point: Determining whether to use lithium or quetiapine in bipolar I and II comes down to side effects.
Major finding: No clinically significant difference was found for bipolar I and bipolar II symptom improvements in patients given lithium or quetiapine (P less than .0001).
Data source: Multicenter, randomized comparative effectiveness study of 482 outpatients on the bipolar spectrum, followed for 6 months as they were given either lithium plus adjunctive therapy, quetiapine plus adjunctive therapy, or monotherapy of either mood stabilizer.
Disclosures: The Agency for Healthcare Research and Quality funded this study in its entirety.
Gold and nickel lead list of eyelid irritants
CHICAGO – Chances are good that if your patient presents with eyelid dermatitis, allergic contact with gold or nickel is the culprit.
"Gold is not thought to be easily released from jewelry, which would be the typical exposure with eyelids, unless it comes into contact with sweat, friction, or abrasives," Dr. Amber Reck Atwater told attendees of a session on facial dermatoses at the American Academy of Dermatology summer meeting.
However, when gold comes into contact with titanium dioxide, a common active ingredient in many cosmetics such as eye shadow, patients are at risk for eyelid irritation.
"If I am wearing a gold ring, and I put this on my eyelids using my finger, the gold will be more easily released, and I will be more likely to get a reaction on my lids," said Dr. Atwater, of the department of dermatology at Duke University, Durham, N.C.
Nickel is another leading cause of eyelid dermatitis, Dr. Atwater said. She warned of the metal’s pernicious tendency to hide in personal care products such as eyelash curlers that do not list it as an active or inactive ingredient.
A simple and relatively inexpensive dimethylglyoxime test, which Dr. Atwater said can be purchased on the consumer market, can help identify items that may contain nickel. Rub a drop of dimethylglyoxime onto an item, such as a house key, with a cotton swab. If the key turns bright pink, then you know it has nickel in it.
"So you can imagine that if I am holding my keys in my hands, I could be transferring nickel from the keys to my eyelids," said Dr. Atwater.
Other potential sources of nickel include faucets, sunglasses with metal frames, barbells, and other weight-lifting equipment.
Other common causes of eyelid dermatitis are products that contain fragrance, including balsam of Peru, neomycin (typically found in antibacterial eye drops), formaldehyde and bronopol (preservatives that are found in certain cosmetics), skin care products, and topicals.
Allergic contact dermatitis in the eyelid can present in an upper, lower, unilateral, or bilateral fashion on the eyelids alone, but typically presents in combination with dermatitis on other areas of the face, or even other areas of the body, according to Dr. Atwater.
"You should be highly suspicious that it’s contact dermatitis when you see eyelid dermatitis with other parts of the body involved," she said.
When the dermatitis presents in the eyelids alone, other factors such as seborrheic dermatitis or aspecific xerotic dermatitis could be the cause.
"Still, a good 30%-50% of our patients will have allergic contact dermatitis when we see them with eyelid dermatitis alone," Dr. Atwater said.
The eyelids are particularly susceptible to irritation in part because the skin is extremely thin – 0.55 mm – compared with other facial areas where the average skin thickness is about 2 mm, Dr. Atwater explained.
"And it’s really easy to transfer substances from our hands to our eyes. People rub their eyes and their faces a lot throughout the day," she noted.
Dr. Atwater had no financial conflicts to disclose.
On Twitter @whitneymcknight
CHICAGO – Chances are good that if your patient presents with eyelid dermatitis, allergic contact with gold or nickel is the culprit.
"Gold is not thought to be easily released from jewelry, which would be the typical exposure with eyelids, unless it comes into contact with sweat, friction, or abrasives," Dr. Amber Reck Atwater told attendees of a session on facial dermatoses at the American Academy of Dermatology summer meeting.
However, when gold comes into contact with titanium dioxide, a common active ingredient in many cosmetics such as eye shadow, patients are at risk for eyelid irritation.
"If I am wearing a gold ring, and I put this on my eyelids using my finger, the gold will be more easily released, and I will be more likely to get a reaction on my lids," said Dr. Atwater, of the department of dermatology at Duke University, Durham, N.C.
Nickel is another leading cause of eyelid dermatitis, Dr. Atwater said. She warned of the metal’s pernicious tendency to hide in personal care products such as eyelash curlers that do not list it as an active or inactive ingredient.
A simple and relatively inexpensive dimethylglyoxime test, which Dr. Atwater said can be purchased on the consumer market, can help identify items that may contain nickel. Rub a drop of dimethylglyoxime onto an item, such as a house key, with a cotton swab. If the key turns bright pink, then you know it has nickel in it.
"So you can imagine that if I am holding my keys in my hands, I could be transferring nickel from the keys to my eyelids," said Dr. Atwater.
Other potential sources of nickel include faucets, sunglasses with metal frames, barbells, and other weight-lifting equipment.
Other common causes of eyelid dermatitis are products that contain fragrance, including balsam of Peru, neomycin (typically found in antibacterial eye drops), formaldehyde and bronopol (preservatives that are found in certain cosmetics), skin care products, and topicals.
Allergic contact dermatitis in the eyelid can present in an upper, lower, unilateral, or bilateral fashion on the eyelids alone, but typically presents in combination with dermatitis on other areas of the face, or even other areas of the body, according to Dr. Atwater.
"You should be highly suspicious that it’s contact dermatitis when you see eyelid dermatitis with other parts of the body involved," she said.
When the dermatitis presents in the eyelids alone, other factors such as seborrheic dermatitis or aspecific xerotic dermatitis could be the cause.
"Still, a good 30%-50% of our patients will have allergic contact dermatitis when we see them with eyelid dermatitis alone," Dr. Atwater said.
The eyelids are particularly susceptible to irritation in part because the skin is extremely thin – 0.55 mm – compared with other facial areas where the average skin thickness is about 2 mm, Dr. Atwater explained.
"And it’s really easy to transfer substances from our hands to our eyes. People rub their eyes and their faces a lot throughout the day," she noted.
Dr. Atwater had no financial conflicts to disclose.
On Twitter @whitneymcknight
CHICAGO – Chances are good that if your patient presents with eyelid dermatitis, allergic contact with gold or nickel is the culprit.
"Gold is not thought to be easily released from jewelry, which would be the typical exposure with eyelids, unless it comes into contact with sweat, friction, or abrasives," Dr. Amber Reck Atwater told attendees of a session on facial dermatoses at the American Academy of Dermatology summer meeting.
However, when gold comes into contact with titanium dioxide, a common active ingredient in many cosmetics such as eye shadow, patients are at risk for eyelid irritation.
"If I am wearing a gold ring, and I put this on my eyelids using my finger, the gold will be more easily released, and I will be more likely to get a reaction on my lids," said Dr. Atwater, of the department of dermatology at Duke University, Durham, N.C.
Nickel is another leading cause of eyelid dermatitis, Dr. Atwater said. She warned of the metal’s pernicious tendency to hide in personal care products such as eyelash curlers that do not list it as an active or inactive ingredient.
A simple and relatively inexpensive dimethylglyoxime test, which Dr. Atwater said can be purchased on the consumer market, can help identify items that may contain nickel. Rub a drop of dimethylglyoxime onto an item, such as a house key, with a cotton swab. If the key turns bright pink, then you know it has nickel in it.
"So you can imagine that if I am holding my keys in my hands, I could be transferring nickel from the keys to my eyelids," said Dr. Atwater.
Other potential sources of nickel include faucets, sunglasses with metal frames, barbells, and other weight-lifting equipment.
Other common causes of eyelid dermatitis are products that contain fragrance, including balsam of Peru, neomycin (typically found in antibacterial eye drops), formaldehyde and bronopol (preservatives that are found in certain cosmetics), skin care products, and topicals.
Allergic contact dermatitis in the eyelid can present in an upper, lower, unilateral, or bilateral fashion on the eyelids alone, but typically presents in combination with dermatitis on other areas of the face, or even other areas of the body, according to Dr. Atwater.
"You should be highly suspicious that it’s contact dermatitis when you see eyelid dermatitis with other parts of the body involved," she said.
When the dermatitis presents in the eyelids alone, other factors such as seborrheic dermatitis or aspecific xerotic dermatitis could be the cause.
"Still, a good 30%-50% of our patients will have allergic contact dermatitis when we see them with eyelid dermatitis alone," Dr. Atwater said.
The eyelids are particularly susceptible to irritation in part because the skin is extremely thin – 0.55 mm – compared with other facial areas where the average skin thickness is about 2 mm, Dr. Atwater explained.
"And it’s really easy to transfer substances from our hands to our eyes. People rub their eyes and their faces a lot throughout the day," she noted.
Dr. Atwater had no financial conflicts to disclose.
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM THE AAD SUMMER ACADEMY 2014
Consider a zero therapy approach to periorificial dermatitis
CHICAGO – For periorificial dermatitis, don’t do a thing. That was the first-line therapy suggested at this year’s American Academy of Dermatology summer meeting.
"Sometimes you have to be brave to tell a patient you’re sending them home with nothing," said Dr. Sarah Wolfe of Duke University in Durham, N.C. "But ‘zero’ therapy is important. It’s simply counseling your patient to recognize the disease and avoid anything that could be exacerbating or precipitating it."
In theory, this advice includes abstinence from using any cosmetics for about 2 months, but "I am not sure whom that will work for," said Dr. Wolfe.
Periorificial dermatitis can affect anyone, but typically occurs in women aged 20-45 years across all ethnicities; it generally presents as erythematous pustules up to 2 mm in size near the nose and mouth, and patients report a burning sensation.
In children, the condition occurs equally in both genders, and tends to peak by age 5 years. Some children develop a distinctive form of the disease – childhood granulomatous periorificial dermatitis – that features persistent, inflammatory papules and pustules that appear symmetrically around the mouth. Although this form tends to be harder to treat and lasts longer, reassure patients that the condition will heal without scarring, Dr. Wolfe said.
Role of steroids
The minimalist approach to treating periorificial dermatitis is particularly important if the condition is related to steroid use, Dr. Wolfe said. Although the prevailing wisdom has been that corticosteroids caused periorificial dermatitis, enough evidence exists to show that corticosteroids likely exacerbate, rather than cause the problem, she explained.
Sometimes patients will use topical steroids (often medications prescribed for other family members or for other ailments) to help calm the burning, unaware of steroids’ potential to make their symptoms worse, she added.
If steroids are implicated, prepare your patient for the possibility of a steroid rebound that lasts a couple of weeks once they stop using the topicals.
"You have to either counsel them through it, or consider using a lower-potency steroid such as a hydrocortisone 2.5% or 1% to get them through that period," Dr. Wolfe said.
Inhaled steroids also have been associated with periorificial dermatitis, occurring where the inhalant mask touches the skin and lips. Intranasal steroids, particularly mometasone furoate and fluticasone furoate, have similarly been associated with the condition in cases of pustules starting near the nose and then spreading to the mouth and chin (Allergy 2001;56:944-8), (Cutan. Ocul. Toxicol. 2012;31:160-3).
Systemic steroids such as prednisone have been associated with the development of periorificial dermatitis upon tapering them, although this association has not been well studied. Because of the risk for the unintentional transfer of topical steroids to the face from other parts of the body being treated, counsel patients to be scrupulous about handwashing after applying their medications, Dr. Wolf emphasized.
Similarly, unintentional corticosteroid use can occur with the use of over the counter skin-lightening products marketed as "herbal" or "all natural," she said.
Oral, topical options
If you and your patient prefer to actively treat the condition, Dr. Wolfe recommended using the most evidence-based therapy available: Oral tetracycline 250-500 mg twice per day, a therapy which showed clearance in 4 to 8 weeks when compared to placebo (G. Ital. Dermatol. Venereol. 2010 Aug;145:433-44).
She did not recommend using this therapy in children younger than 8 years, because of the drug’s association with dental abnormalities. Other antibiotics such as doxycycline, minocycline, and azithromycin (in children) have not been well studied, Dr. Wolfe said, although she noted anecdotal reports of pediatric dermatologists prescribing azithromycin if the patient’s presentation is "slightly disfiguring."
Although erythromycin may be easier to use when controlling costs, both it and pimecrolimus are viable options for topical therapy, Dr. Wolfe said. Pimecrolimus 1% cream has been shown to reduce disease severity in 2 weeks, while erythromycin 2% solution, in ointment or gel form twice daily, brought clearance in 3-7 weeks in a randomized, placebo-controlled trial. She emphasized the importance of discussing all topical exposures with patients, regardless of the treatment option chosen.
Dr. Wolfe had no financial conflicts to disclose.
On Twitter @whitneymcknight
CHICAGO – For periorificial dermatitis, don’t do a thing. That was the first-line therapy suggested at this year’s American Academy of Dermatology summer meeting.
"Sometimes you have to be brave to tell a patient you’re sending them home with nothing," said Dr. Sarah Wolfe of Duke University in Durham, N.C. "But ‘zero’ therapy is important. It’s simply counseling your patient to recognize the disease and avoid anything that could be exacerbating or precipitating it."
In theory, this advice includes abstinence from using any cosmetics for about 2 months, but "I am not sure whom that will work for," said Dr. Wolfe.
Periorificial dermatitis can affect anyone, but typically occurs in women aged 20-45 years across all ethnicities; it generally presents as erythematous pustules up to 2 mm in size near the nose and mouth, and patients report a burning sensation.
In children, the condition occurs equally in both genders, and tends to peak by age 5 years. Some children develop a distinctive form of the disease – childhood granulomatous periorificial dermatitis – that features persistent, inflammatory papules and pustules that appear symmetrically around the mouth. Although this form tends to be harder to treat and lasts longer, reassure patients that the condition will heal without scarring, Dr. Wolfe said.
Role of steroids
The minimalist approach to treating periorificial dermatitis is particularly important if the condition is related to steroid use, Dr. Wolfe said. Although the prevailing wisdom has been that corticosteroids caused periorificial dermatitis, enough evidence exists to show that corticosteroids likely exacerbate, rather than cause the problem, she explained.
Sometimes patients will use topical steroids (often medications prescribed for other family members or for other ailments) to help calm the burning, unaware of steroids’ potential to make their symptoms worse, she added.
If steroids are implicated, prepare your patient for the possibility of a steroid rebound that lasts a couple of weeks once they stop using the topicals.
"You have to either counsel them through it, or consider using a lower-potency steroid such as a hydrocortisone 2.5% or 1% to get them through that period," Dr. Wolfe said.
Inhaled steroids also have been associated with periorificial dermatitis, occurring where the inhalant mask touches the skin and lips. Intranasal steroids, particularly mometasone furoate and fluticasone furoate, have similarly been associated with the condition in cases of pustules starting near the nose and then spreading to the mouth and chin (Allergy 2001;56:944-8), (Cutan. Ocul. Toxicol. 2012;31:160-3).
Systemic steroids such as prednisone have been associated with the development of periorificial dermatitis upon tapering them, although this association has not been well studied. Because of the risk for the unintentional transfer of topical steroids to the face from other parts of the body being treated, counsel patients to be scrupulous about handwashing after applying their medications, Dr. Wolf emphasized.
Similarly, unintentional corticosteroid use can occur with the use of over the counter skin-lightening products marketed as "herbal" or "all natural," she said.
Oral, topical options
If you and your patient prefer to actively treat the condition, Dr. Wolfe recommended using the most evidence-based therapy available: Oral tetracycline 250-500 mg twice per day, a therapy which showed clearance in 4 to 8 weeks when compared to placebo (G. Ital. Dermatol. Venereol. 2010 Aug;145:433-44).
She did not recommend using this therapy in children younger than 8 years, because of the drug’s association with dental abnormalities. Other antibiotics such as doxycycline, minocycline, and azithromycin (in children) have not been well studied, Dr. Wolfe said, although she noted anecdotal reports of pediatric dermatologists prescribing azithromycin if the patient’s presentation is "slightly disfiguring."
Although erythromycin may be easier to use when controlling costs, both it and pimecrolimus are viable options for topical therapy, Dr. Wolfe said. Pimecrolimus 1% cream has been shown to reduce disease severity in 2 weeks, while erythromycin 2% solution, in ointment or gel form twice daily, brought clearance in 3-7 weeks in a randomized, placebo-controlled trial. She emphasized the importance of discussing all topical exposures with patients, regardless of the treatment option chosen.
Dr. Wolfe had no financial conflicts to disclose.
On Twitter @whitneymcknight
CHICAGO – For periorificial dermatitis, don’t do a thing. That was the first-line therapy suggested at this year’s American Academy of Dermatology summer meeting.
"Sometimes you have to be brave to tell a patient you’re sending them home with nothing," said Dr. Sarah Wolfe of Duke University in Durham, N.C. "But ‘zero’ therapy is important. It’s simply counseling your patient to recognize the disease and avoid anything that could be exacerbating or precipitating it."
In theory, this advice includes abstinence from using any cosmetics for about 2 months, but "I am not sure whom that will work for," said Dr. Wolfe.
Periorificial dermatitis can affect anyone, but typically occurs in women aged 20-45 years across all ethnicities; it generally presents as erythematous pustules up to 2 mm in size near the nose and mouth, and patients report a burning sensation.
In children, the condition occurs equally in both genders, and tends to peak by age 5 years. Some children develop a distinctive form of the disease – childhood granulomatous periorificial dermatitis – that features persistent, inflammatory papules and pustules that appear symmetrically around the mouth. Although this form tends to be harder to treat and lasts longer, reassure patients that the condition will heal without scarring, Dr. Wolfe said.
Role of steroids
The minimalist approach to treating periorificial dermatitis is particularly important if the condition is related to steroid use, Dr. Wolfe said. Although the prevailing wisdom has been that corticosteroids caused periorificial dermatitis, enough evidence exists to show that corticosteroids likely exacerbate, rather than cause the problem, she explained.
Sometimes patients will use topical steroids (often medications prescribed for other family members or for other ailments) to help calm the burning, unaware of steroids’ potential to make their symptoms worse, she added.
If steroids are implicated, prepare your patient for the possibility of a steroid rebound that lasts a couple of weeks once they stop using the topicals.
"You have to either counsel them through it, or consider using a lower-potency steroid such as a hydrocortisone 2.5% or 1% to get them through that period," Dr. Wolfe said.
Inhaled steroids also have been associated with periorificial dermatitis, occurring where the inhalant mask touches the skin and lips. Intranasal steroids, particularly mometasone furoate and fluticasone furoate, have similarly been associated with the condition in cases of pustules starting near the nose and then spreading to the mouth and chin (Allergy 2001;56:944-8), (Cutan. Ocul. Toxicol. 2012;31:160-3).
Systemic steroids such as prednisone have been associated with the development of periorificial dermatitis upon tapering them, although this association has not been well studied. Because of the risk for the unintentional transfer of topical steroids to the face from other parts of the body being treated, counsel patients to be scrupulous about handwashing after applying their medications, Dr. Wolf emphasized.
Similarly, unintentional corticosteroid use can occur with the use of over the counter skin-lightening products marketed as "herbal" or "all natural," she said.
Oral, topical options
If you and your patient prefer to actively treat the condition, Dr. Wolfe recommended using the most evidence-based therapy available: Oral tetracycline 250-500 mg twice per day, a therapy which showed clearance in 4 to 8 weeks when compared to placebo (G. Ital. Dermatol. Venereol. 2010 Aug;145:433-44).
She did not recommend using this therapy in children younger than 8 years, because of the drug’s association with dental abnormalities. Other antibiotics such as doxycycline, minocycline, and azithromycin (in children) have not been well studied, Dr. Wolfe said, although she noted anecdotal reports of pediatric dermatologists prescribing azithromycin if the patient’s presentation is "slightly disfiguring."
Although erythromycin may be easier to use when controlling costs, both it and pimecrolimus are viable options for topical therapy, Dr. Wolfe said. Pimecrolimus 1% cream has been shown to reduce disease severity in 2 weeks, while erythromycin 2% solution, in ointment or gel form twice daily, brought clearance in 3-7 weeks in a randomized, placebo-controlled trial. She emphasized the importance of discussing all topical exposures with patients, regardless of the treatment option chosen.
Dr. Wolfe had no financial conflicts to disclose.
On Twitter @whitneymcknight
EXPERT ANALYSIS FROM THE AAD SUMMER ACADEMY 2014
