Pulmonary Health Hub

Introduction of two specific variations of pneumococcal conjugate vaccine in children no older than 5 years of age can decrease their chances of developing sinusitis and pneumonia, according to a new study published in Pediatrics (Pediatrics 2014 doi: 10.1542/peds.2013-4177).

“Streptococcus pneumoniae is a major cause of pneumonia and sinusitis,” according to Dr. Ann Lindstrand, of the Public Health Agency of Sweden in Solna, and her associates “Although pneumococcal conjugate vaccine (PCV) is effective against invasive pneumococcal disease, its effectiveness against pneumonia is less consistent, and its effect on sinusitis is not known.”

Courtesy NIH National Library of Medicine / Institute for Physical Education and Sport, University of Malta, Malta / Creative Commons License

The retrospective, population-based study involved data from three pediatric hospitals in Stockholm County, Sweden. The investigators compared the incidence of sinusitis, pneumonia, and empyema in the years July 2003 to June 2007 with the years July 2008 to June 2012, excluding the year of PCV7 introduction.

The results showed that PCV7 and PCV13 vaccinations led to significant decreases in sinusitis and pneumonia cases for children at or under the age of 2, while a decrease, though less profound, was also noted in cases of sinusitis and pneumonia for children between 2 and 5 years of age.

Following the introduction of PCV7 and PCV13 vaccinations, incidences of sinusitis dropped from 70 cases per 100,000 person-years to 24 cases per 100,000 for children ages 0-2 years (RR = 0.34, P < .001), while incidences for children ages 2-5 years dropped from 25 cases per 100,000 person-years to 18 cases per 100,000 person-years (RR = 0.76, P = 0.06). In cases of pneumonia, children ages 0-2 years saw incidence drop from 450 cases to 366 cases per 100,000 person-years (RR = 0.81, P , .001), while incidences in children ages 2-5 years decreased from 250 cases to 212 cases per 100,000 person-years (RR = 0.85, P = .002).

However, for children ages 5-18 years who received the vaccinations, hospitalizations for both sinusitis and pneumonia increased, albeit marginally. Similar increases were also noted in children who received the vaccines and developed empyema across all three age brackets. The increase in empyema hospitalizations as “not statistically significant,” according to Dr. Lindstrand and her associates.

“Pneumococcal disease is the most important vaccine-preventable disease in children, because it causes most child deaths. Many low- and middle-income countries are implementing PCV vaccination programs,” the study says. “This study adds evidence that PCV vaccine (PCV7 and PCV13) prevents severe sinusitis and pneumonia, with implications for global child survival. Specifically, we are the first to show great effectiveness against sinusitis in children [under] 5 years [of age].”

The authors reported that this study was supported by Stockholm County Council research funds, Foundation Samariten, Sachs’ Children’s Hospital, Swedish Research Council, Swedish Foundation for Strategic Research, Knut and Alice Wallenberg Foundation, and Sven Jerrings Foundation, Furthermore, the Stockholm County Council required that the company chosen to supply the vaccine was to give the county a 5% discount off the vaccine price for enabling an epidemiologic follow-up. Finally, Dr. Lindstrand disclosed that she received financial contributions for participation in two scientific conferences from GSK and Pfizer, with her employer financing the equivalent amount in accordance with Swedish rules for pharmaceutical sponsorship for medical education. She has also participated in one clinical vaccine trial in collaboration with GSK.

dchitnis@frontlinemedcom.com

Introduction of two specific variations of pneumococcal conjugate vaccine in children no older than 5 years of age can decrease their chances of developing sinusitis and pneumonia, according to a new study published in Pediatrics (Pediatrics 2014 doi: 10.1542/peds.2013-4177).

“Streptococcus pneumoniae is a major cause of pneumonia and sinusitis,” according to Dr. Ann Lindstrand, of the Public Health Agency of Sweden in Solna, and her associates “Although pneumococcal conjugate vaccine (PCV) is effective against invasive pneumococcal disease, its effectiveness against pneumonia is less consistent, and its effect on sinusitis is not known.”

Courtesy NIH National Library of Medicine / Institute for Physical Education and Sport, University of Malta, Malta / Creative Commons License

The retrospective, population-based study involved data from three pediatric hospitals in Stockholm County, Sweden. The investigators compared the incidence of sinusitis, pneumonia, and empyema in the years July 2003 to June 2007 with the years July 2008 to June 2012, excluding the year of PCV7 introduction.

The results showed that PCV7 and PCV13 vaccinations led to significant decreases in sinusitis and pneumonia cases for children at or under the age of 2, while a decrease, though less profound, was also noted in cases of sinusitis and pneumonia for children between 2 and 5 years of age.

Following the introduction of PCV7 and PCV13 vaccinations, incidences of sinusitis dropped from 70 cases per 100,000 person-years to 24 cases per 100,000 for children ages 0-2 years (RR = 0.34, P < .001), while incidences for children ages 2-5 years dropped from 25 cases per 100,000 person-years to 18 cases per 100,000 person-years (RR = 0.76, P = 0.06). In cases of pneumonia, children ages 0-2 years saw incidence drop from 450 cases to 366 cases per 100,000 person-years (RR = 0.81, P , .001), while incidences in children ages 2-5 years decreased from 250 cases to 212 cases per 100,000 person-years (RR = 0.85, P = .002).

However, for children ages 5-18 years who received the vaccinations, hospitalizations for both sinusitis and pneumonia increased, albeit marginally. Similar increases were also noted in children who received the vaccines and developed empyema across all three age brackets. The increase in empyema hospitalizations as “not statistically significant,” according to Dr. Lindstrand and her associates.

“Pneumococcal disease is the most important vaccine-preventable disease in children, because it causes most child deaths. Many low- and middle-income countries are implementing PCV vaccination programs,” the study says. “This study adds evidence that PCV vaccine (PCV7 and PCV13) prevents severe sinusitis and pneumonia, with implications for global child survival. Specifically, we are the first to show great effectiveness against sinusitis in children [under] 5 years [of age].”

The authors reported that this study was supported by Stockholm County Council research funds, Foundation Samariten, Sachs’ Children’s Hospital, Swedish Research Council, Swedish Foundation for Strategic Research, Knut and Alice Wallenberg Foundation, and Sven Jerrings Foundation, Furthermore, the Stockholm County Council required that the company chosen to supply the vaccine was to give the county a 5% discount off the vaccine price for enabling an epidemiologic follow-up. Finally, Dr. Lindstrand disclosed that she received financial contributions for participation in two scientific conferences from GSK and Pfizer, with her employer financing the equivalent amount in accordance with Swedish rules for pharmaceutical sponsorship for medical education. She has also participated in one clinical vaccine trial in collaboration with GSK.

dchitnis@frontlinemedcom.com

Introduction of two specific variations of pneumococcal conjugate vaccine in children no older than 5 years of age can decrease their chances of developing sinusitis and pneumonia, according to a new study published in Pediatrics (Pediatrics 2014 doi: 10.1542/peds.2013-4177).

“Streptococcus pneumoniae is a major cause of pneumonia and sinusitis,” according to Dr. Ann Lindstrand, of the Public Health Agency of Sweden in Solna, and her associates “Although pneumococcal conjugate vaccine (PCV) is effective against invasive pneumococcal disease, its effectiveness against pneumonia is less consistent, and its effect on sinusitis is not known.”

Courtesy NIH National Library of Medicine / Institute for Physical Education and Sport, University of Malta, Malta / Creative Commons License

The retrospective, population-based study involved data from three pediatric hospitals in Stockholm County, Sweden. The investigators compared the incidence of sinusitis, pneumonia, and empyema in the years July 2003 to June 2007 with the years July 2008 to June 2012, excluding the year of PCV7 introduction.

The results showed that PCV7 and PCV13 vaccinations led to significant decreases in sinusitis and pneumonia cases for children at or under the age of 2, while a decrease, though less profound, was also noted in cases of sinusitis and pneumonia for children between 2 and 5 years of age.

Following the introduction of PCV7 and PCV13 vaccinations, incidences of sinusitis dropped from 70 cases per 100,000 person-years to 24 cases per 100,000 for children ages 0-2 years (RR = 0.34, P < .001), while incidences for children ages 2-5 years dropped from 25 cases per 100,000 person-years to 18 cases per 100,000 person-years (RR = 0.76, P = 0.06). In cases of pneumonia, children ages 0-2 years saw incidence drop from 450 cases to 366 cases per 100,000 person-years (RR = 0.81, P , .001), while incidences in children ages 2-5 years decreased from 250 cases to 212 cases per 100,000 person-years (RR = 0.85, P = .002).

However, for children ages 5-18 years who received the vaccinations, hospitalizations for both sinusitis and pneumonia increased, albeit marginally. Similar increases were also noted in children who received the vaccines and developed empyema across all three age brackets. The increase in empyema hospitalizations as “not statistically significant,” according to Dr. Lindstrand and her associates.

“Pneumococcal disease is the most important vaccine-preventable disease in children, because it causes most child deaths. Many low- and middle-income countries are implementing PCV vaccination programs,” the study says. “This study adds evidence that PCV vaccine (PCV7 and PCV13) prevents severe sinusitis and pneumonia, with implications for global child survival. Specifically, we are the first to show great effectiveness against sinusitis in children [under] 5 years [of age].”

The authors reported that this study was supported by Stockholm County Council research funds, Foundation Samariten, Sachs’ Children’s Hospital, Swedish Research Council, Swedish Foundation for Strategic Research, Knut and Alice Wallenberg Foundation, and Sven Jerrings Foundation, Furthermore, the Stockholm County Council required that the company chosen to supply the vaccine was to give the county a 5% discount off the vaccine price for enabling an epidemiologic follow-up. Finally, Dr. Lindstrand disclosed that she received financial contributions for participation in two scientific conferences from GSK and Pfizer, with her employer financing the equivalent amount in accordance with Swedish rules for pharmaceutical sponsorship for medical education. She has also participated in one clinical vaccine trial in collaboration with GSK.

dchitnis@frontlinemedcom.com

Children with obstructive sleep apnea appear to gain moderate cardiac benefits based on echocardiographic findings following an adenotonsillectomy, according to a recent meta-analysis.

“This review showed cardiovascular repercussions mostly on pulmonary circulation, right heart dimensions and diastolic function, with improvement after treatment,” Dr. Silke Anna Theresa Weber of Universidade Estadual Paulisita–UNESP in Botucatu, Brazil, and her colleagues reported (Int. J. Pediatr. Otorhinolaryngol. 2014;78:1571-8).

From a search of PUBMED, Embase, and LILACS in studies of cohorts ranging from 55 to 110 subjects, the researchers identified seven cohort studies meeting their criteria. Each study included children 12 years old or younger with obstructive sleep apnea (OSA) who received an adenotonsillectomy, and a comparison group of children without OSA.

Before the surgery, children with OSA had 8.67 greater mean pulmonary arterial pressure levels, compared with those without OSA, according to data in two studies. After surgery, the groups’ levels did not differ with statistical significance. Preoperatively, children with OSA had a mean 0.60-mm thicker increased interventricular septum and a mean 0.19-cm/m right ventricular dimension, compared with children with OSA in those two studies.

After the operation through 6 months’ follow-up, two studies “showed improvement of the mean arterial pulmonary blood pressure” in OSA children, and three other studies “showed improvement of cardiac structure and heart functions, mostly on the right heart, as right ventricle dimensions, tricuspid E/A ratio, and estimated pulmonary pressure,” the authors wrote.

Yet, the evidence for postoperative positive cardiovascular outcomes were limited, the authors wrote. None of the studies mentioned confounding factors for cardiovascular disease, such as obesity, and many did not use polysomnography for sleep apnea diagnoses.

The study was supported by FAPESP – Fundação de Amparo á Pesquisa do Estado de São Paulo. The authors reported no disclosures.

Children with obstructive sleep apnea appear to gain moderate cardiac benefits based on echocardiographic findings following an adenotonsillectomy, according to a recent meta-analysis.

“This review showed cardiovascular repercussions mostly on pulmonary circulation, right heart dimensions and diastolic function, with improvement after treatment,” Dr. Silke Anna Theresa Weber of Universidade Estadual Paulisita–UNESP in Botucatu, Brazil, and her colleagues reported (Int. J. Pediatr. Otorhinolaryngol. 2014;78:1571-8).

From a search of PUBMED, Embase, and LILACS in studies of cohorts ranging from 55 to 110 subjects, the researchers identified seven cohort studies meeting their criteria. Each study included children 12 years old or younger with obstructive sleep apnea (OSA) who received an adenotonsillectomy, and a comparison group of children without OSA.

Before the surgery, children with OSA had 8.67 greater mean pulmonary arterial pressure levels, compared with those without OSA, according to data in two studies. After surgery, the groups’ levels did not differ with statistical significance. Preoperatively, children with OSA had a mean 0.60-mm thicker increased interventricular septum and a mean 0.19-cm/m right ventricular dimension, compared with children with OSA in those two studies.

After the operation through 6 months’ follow-up, two studies “showed improvement of the mean arterial pulmonary blood pressure” in OSA children, and three other studies “showed improvement of cardiac structure and heart functions, mostly on the right heart, as right ventricle dimensions, tricuspid E/A ratio, and estimated pulmonary pressure,” the authors wrote.

Yet, the evidence for postoperative positive cardiovascular outcomes were limited, the authors wrote. None of the studies mentioned confounding factors for cardiovascular disease, such as obesity, and many did not use polysomnography for sleep apnea diagnoses.

The study was supported by FAPESP – Fundação de Amparo á Pesquisa do Estado de São Paulo. The authors reported no disclosures.

Children with obstructive sleep apnea appear to gain moderate cardiac benefits based on echocardiographic findings following an adenotonsillectomy, according to a recent meta-analysis.

“This review showed cardiovascular repercussions mostly on pulmonary circulation, right heart dimensions and diastolic function, with improvement after treatment,” Dr. Silke Anna Theresa Weber of Universidade Estadual Paulisita–UNESP in Botucatu, Brazil, and her colleagues reported (Int. J. Pediatr. Otorhinolaryngol. 2014;78:1571-8).

From a search of PUBMED, Embase, and LILACS in studies of cohorts ranging from 55 to 110 subjects, the researchers identified seven cohort studies meeting their criteria. Each study included children 12 years old or younger with obstructive sleep apnea (OSA) who received an adenotonsillectomy, and a comparison group of children without OSA.

Before the surgery, children with OSA had 8.67 greater mean pulmonary arterial pressure levels, compared with those without OSA, according to data in two studies. After surgery, the groups’ levels did not differ with statistical significance. Preoperatively, children with OSA had a mean 0.60-mm thicker increased interventricular septum and a mean 0.19-cm/m right ventricular dimension, compared with children with OSA in those two studies.

After the operation through 6 months’ follow-up, two studies “showed improvement of the mean arterial pulmonary blood pressure” in OSA children, and three other studies “showed improvement of cardiac structure and heart functions, mostly on the right heart, as right ventricle dimensions, tricuspid E/A ratio, and estimated pulmonary pressure,” the authors wrote.

Yet, the evidence for postoperative positive cardiovascular outcomes were limited, the authors wrote. None of the studies mentioned confounding factors for cardiovascular disease, such as obesity, and many did not use polysomnography for sleep apnea diagnoses.

The study was supported by FAPESP – Fundação de Amparo á Pesquisa do Estado de São Paulo. The authors reported no disclosures.

PHILADELPHIA – Brincidofovir, an orally available lipid conjugate of cidofovir, appears promising for the treatment of adenovirus infection in children and young adults, according to findings from the open-label pilot portion of a phase III study.

Of 26 patients from birth through age 29 years who were enrolled in the study as of July 15, 13 discontinued treatment prematurely, 4 completed treatment, and 9 continued with treatment. Plasma viral load decreased over time in most of the 13 patients who either completed or remained on treatment, Dr. Jo-Anne Young reported at an annual scientific meeting on infectious diseases.

After a median treatment duration of 54 days, clearance of adenovirus from respiratory secretions, urine, and stool among those patients in whom these values were measured at baseline was 42%, 33%, and 27%, respectively. Mortality was 46% among all 26 patients and was 38% among patients with disseminated disease. In a prior expanded-access trial of the drug, mortality was 51% in treated patients with disseminated disease, and in a historical cohort from a 2003 study of patients with disseminated disease, mortality at 1 year was 82%.

Of note, one patient in the current study experienced an increase in viral load; that patient had received prior treatment with brincidofovir, and was found to have a T87I mutation with known resistance to cidofovir and brincidofovir. Six other patients with prior cidofovir exposure reached undetectable levels of adenovirus, and one had a greater than 2-log decline, so the effect of prior exposure on treatment response remains uncertain, Dr. Young of the University of Minnesota Medical Center, Minneapolis, said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Another trend that was noted in the current study was a possible increase in viral load prior to a decline in viral load. In one case this occurred in association with treatment interruption due to moderate hyperbilirubinemia, but the viral load declined again once treatment was restarted, and was undetectable by the 8th week of treatment.

Most of the patients in the study to date (80%) were children, 65% were males, 65% were white, and 65% had disseminated infection with two or more body systems affected. Most of those were high-risk patients, who had received hematopoietic stem cell transplants from unrelated donors, Dr. Young noted.

Half of the patients had a high viral copy load in their blood, and many had multiple viruses detected. For example, 27% had BK virus in their urine, 19% had cytomegalovirus detected in their plasma, and 8% had Epstein-Barr virus detected in their plasma .

Treatment was given as a twice-weekly 100-mg dose in adults weighing at least 50 kg, and as a twice-weekly, 2-mg/kg dose in children under age 12 or weighing less than 50 kg. Treatment duration was 12 weeks, and patients were followed for an additional 24 weeks.

Of the 13 patients who discontinued treatment, 4 died, 3 discontinued because of an adverse event (including 2 cases of diarrhea considered treatment related and 1 case of liver function testing abnormalities deemed unrelated to treatment), 2 discontinued on physician advice, 2 started other therapy, 1 experienced progression of transplant qualifying disease, and 1 withdrew consent for study participation. Among those who continued, median treatment duration was 54 days at the time the data were presented.

“Adenovirus is an infection with a high unmet medical treatment need,” Dr. Young said, noting that it is associated with a wide spectrum of disease, ranging from asymptomatic viremia to disseminated disease, particularly among hematopoietic stem cell transplant recipients.

The reported incidence varies from 5% to 50%, and mortality ranges from 26% for untreated symptomatic infection to 80% for disseminated disease.

Risk factors include pediatric age, high-risk types of allogeneic transplants, and the presence of acute graft vs. host disease in any transplant recipient.

Current treatment strategies involve supportive care with a reduction in immune suppression and/or initiation of direct antiviral treatment – typically intravenous cidofovir, which is associated with a risk of significant renal injury, Dr. Young said.

Brincidofovir, however, allows for oral dosing and high intracellular uptake, delivering high intracellular levels of the active antiviral, she noted, adding that there is no evidence of nephrotoxicity or hematologic toxicity associated with brincidofovir.

Antiadenovirus activity was confirmed in a previous study of the drug, and in the expanded-access study, treatment was associated with improved survival vs. historical data.

Up to 100 patients will be enrolled in the current pilot portion of the study, and the findings will be used to guide the second half of the phase III study, she said, noting that as of September, 48 subjects from 17 centers had been enrolled.

“Brincidofovir demonstrated potent virologic activity in patients with adenovirus disease. Subjects treated with brincidofovir appeared to have improved survival vs. historical controls, and there were no new safety signals identified. The data from the pilot portion of this study clearly support progression to the design of the next half of this phase III study for brincidofovir among adenovirus-infected patients,” she concluded.

Dr. Young reported being a clinical investigator and/or receiving research support from Chimerix, GlaxoSmithKline, Merck, and ViroPharma.

PHILADELPHIA – Brincidofovir, an orally available lipid conjugate of cidofovir, appears promising for the treatment of adenovirus infection in children and young adults, according to findings from the open-label pilot portion of a phase III study.

Of 26 patients from birth through age 29 years who were enrolled in the study as of July 15, 13 discontinued treatment prematurely, 4 completed treatment, and 9 continued with treatment. Plasma viral load decreased over time in most of the 13 patients who either completed or remained on treatment, Dr. Jo-Anne Young reported at an annual scientific meeting on infectious diseases.

After a median treatment duration of 54 days, clearance of adenovirus from respiratory secretions, urine, and stool among those patients in whom these values were measured at baseline was 42%, 33%, and 27%, respectively. Mortality was 46% among all 26 patients and was 38% among patients with disseminated disease. In a prior expanded-access trial of the drug, mortality was 51% in treated patients with disseminated disease, and in a historical cohort from a 2003 study of patients with disseminated disease, mortality at 1 year was 82%.

Of note, one patient in the current study experienced an increase in viral load; that patient had received prior treatment with brincidofovir, and was found to have a T87I mutation with known resistance to cidofovir and brincidofovir. Six other patients with prior cidofovir exposure reached undetectable levels of adenovirus, and one had a greater than 2-log decline, so the effect of prior exposure on treatment response remains uncertain, Dr. Young of the University of Minnesota Medical Center, Minneapolis, said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Another trend that was noted in the current study was a possible increase in viral load prior to a decline in viral load. In one case this occurred in association with treatment interruption due to moderate hyperbilirubinemia, but the viral load declined again once treatment was restarted, and was undetectable by the 8th week of treatment.

Most of the patients in the study to date (80%) were children, 65% were males, 65% were white, and 65% had disseminated infection with two or more body systems affected. Most of those were high-risk patients, who had received hematopoietic stem cell transplants from unrelated donors, Dr. Young noted.

Half of the patients had a high viral copy load in their blood, and many had multiple viruses detected. For example, 27% had BK virus in their urine, 19% had cytomegalovirus detected in their plasma, and 8% had Epstein-Barr virus detected in their plasma .

Treatment was given as a twice-weekly 100-mg dose in adults weighing at least 50 kg, and as a twice-weekly, 2-mg/kg dose in children under age 12 or weighing less than 50 kg. Treatment duration was 12 weeks, and patients were followed for an additional 24 weeks.

Of the 13 patients who discontinued treatment, 4 died, 3 discontinued because of an adverse event (including 2 cases of diarrhea considered treatment related and 1 case of liver function testing abnormalities deemed unrelated to treatment), 2 discontinued on physician advice, 2 started other therapy, 1 experienced progression of transplant qualifying disease, and 1 withdrew consent for study participation. Among those who continued, median treatment duration was 54 days at the time the data were presented.

“Adenovirus is an infection with a high unmet medical treatment need,” Dr. Young said, noting that it is associated with a wide spectrum of disease, ranging from asymptomatic viremia to disseminated disease, particularly among hematopoietic stem cell transplant recipients.

The reported incidence varies from 5% to 50%, and mortality ranges from 26% for untreated symptomatic infection to 80% for disseminated disease.

Risk factors include pediatric age, high-risk types of allogeneic transplants, and the presence of acute graft vs. host disease in any transplant recipient.

Current treatment strategies involve supportive care with a reduction in immune suppression and/or initiation of direct antiviral treatment – typically intravenous cidofovir, which is associated with a risk of significant renal injury, Dr. Young said.

Brincidofovir, however, allows for oral dosing and high intracellular uptake, delivering high intracellular levels of the active antiviral, she noted, adding that there is no evidence of nephrotoxicity or hematologic toxicity associated with brincidofovir.

Antiadenovirus activity was confirmed in a previous study of the drug, and in the expanded-access study, treatment was associated with improved survival vs. historical data.

Up to 100 patients will be enrolled in the current pilot portion of the study, and the findings will be used to guide the second half of the phase III study, she said, noting that as of September, 48 subjects from 17 centers had been enrolled.

“Brincidofovir demonstrated potent virologic activity in patients with adenovirus disease. Subjects treated with brincidofovir appeared to have improved survival vs. historical controls, and there were no new safety signals identified. The data from the pilot portion of this study clearly support progression to the design of the next half of this phase III study for brincidofovir among adenovirus-infected patients,” she concluded.

Dr. Young reported being a clinical investigator and/or receiving research support from Chimerix, GlaxoSmithKline, Merck, and ViroPharma.

PHILADELPHIA – Brincidofovir, an orally available lipid conjugate of cidofovir, appears promising for the treatment of adenovirus infection in children and young adults, according to findings from the open-label pilot portion of a phase III study.

Of 26 patients from birth through age 29 years who were enrolled in the study as of July 15, 13 discontinued treatment prematurely, 4 completed treatment, and 9 continued with treatment. Plasma viral load decreased over time in most of the 13 patients who either completed or remained on treatment, Dr. Jo-Anne Young reported at an annual scientific meeting on infectious diseases.

After a median treatment duration of 54 days, clearance of adenovirus from respiratory secretions, urine, and stool among those patients in whom these values were measured at baseline was 42%, 33%, and 27%, respectively. Mortality was 46% among all 26 patients and was 38% among patients with disseminated disease. In a prior expanded-access trial of the drug, mortality was 51% in treated patients with disseminated disease, and in a historical cohort from a 2003 study of patients with disseminated disease, mortality at 1 year was 82%.

Of note, one patient in the current study experienced an increase in viral load; that patient had received prior treatment with brincidofovir, and was found to have a T87I mutation with known resistance to cidofovir and brincidofovir. Six other patients with prior cidofovir exposure reached undetectable levels of adenovirus, and one had a greater than 2-log decline, so the effect of prior exposure on treatment response remains uncertain, Dr. Young of the University of Minnesota Medical Center, Minneapolis, said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

Another trend that was noted in the current study was a possible increase in viral load prior to a decline in viral load. In one case this occurred in association with treatment interruption due to moderate hyperbilirubinemia, but the viral load declined again once treatment was restarted, and was undetectable by the 8th week of treatment.

Most of the patients in the study to date (80%) were children, 65% were males, 65% were white, and 65% had disseminated infection with two or more body systems affected. Most of those were high-risk patients, who had received hematopoietic stem cell transplants from unrelated donors, Dr. Young noted.

Half of the patients had a high viral copy load in their blood, and many had multiple viruses detected. For example, 27% had BK virus in their urine, 19% had cytomegalovirus detected in their plasma, and 8% had Epstein-Barr virus detected in their plasma .

Treatment was given as a twice-weekly 100-mg dose in adults weighing at least 50 kg, and as a twice-weekly, 2-mg/kg dose in children under age 12 or weighing less than 50 kg. Treatment duration was 12 weeks, and patients were followed for an additional 24 weeks.

Of the 13 patients who discontinued treatment, 4 died, 3 discontinued because of an adverse event (including 2 cases of diarrhea considered treatment related and 1 case of liver function testing abnormalities deemed unrelated to treatment), 2 discontinued on physician advice, 2 started other therapy, 1 experienced progression of transplant qualifying disease, and 1 withdrew consent for study participation. Among those who continued, median treatment duration was 54 days at the time the data were presented.

“Adenovirus is an infection with a high unmet medical treatment need,” Dr. Young said, noting that it is associated with a wide spectrum of disease, ranging from asymptomatic viremia to disseminated disease, particularly among hematopoietic stem cell transplant recipients.

The reported incidence varies from 5% to 50%, and mortality ranges from 26% for untreated symptomatic infection to 80% for disseminated disease.

Risk factors include pediatric age, high-risk types of allogeneic transplants, and the presence of acute graft vs. host disease in any transplant recipient.

Current treatment strategies involve supportive care with a reduction in immune suppression and/or initiation of direct antiviral treatment – typically intravenous cidofovir, which is associated with a risk of significant renal injury, Dr. Young said.

Brincidofovir, however, allows for oral dosing and high intracellular uptake, delivering high intracellular levels of the active antiviral, she noted, adding that there is no evidence of nephrotoxicity or hematologic toxicity associated with brincidofovir.

Antiadenovirus activity was confirmed in a previous study of the drug, and in the expanded-access study, treatment was associated with improved survival vs. historical data.

Up to 100 patients will be enrolled in the current pilot portion of the study, and the findings will be used to guide the second half of the phase III study, she said, noting that as of September, 48 subjects from 17 centers had been enrolled.

“Brincidofovir demonstrated potent virologic activity in patients with adenovirus disease. Subjects treated with brincidofovir appeared to have improved survival vs. historical controls, and there were no new safety signals identified. The data from the pilot portion of this study clearly support progression to the design of the next half of this phase III study for brincidofovir among adenovirus-infected patients,” she concluded.

Dr. Young reported being a clinical investigator and/or receiving research support from Chimerix, GlaxoSmithKline, Merck, and ViroPharma.

PHILADELPHIA – ALS-008176, an oral prodrug of the novel cytidine nucleoside analog, rapidly reduced respiratory syncitial virus load and clinical disease severity in healthy adult volunteers infected with a clinical strain of the virus as part of a double-blind, placebo-controlled phase IIa study.

Of 62 adults aged 18-45 years with preexisting RSV-A specific antibody titers who were inoculated with RSV-A Memphis 37b virus and randomized to receive placebo or one of three ALS-008176 dosing regimens, 35 met the criteria for infection. The viral load area under the curve (AUC) was significantly and rapidly reduced in all volunteers who received ALS-008176, compared with those who received placebo; the reduction in AUC, compared with placebo, ranged from 73% to 88% for the treatment groups at day 12 , Dr. John DeVincenzo of the University of Tennessee Health Science Center, Memphis, reported at an annual scientific meeting on infectious diseases.

Further, the AUC for symptom scores and mucous quantity as measured by weight were also reduced for all treatment groups, compared with placebo, and no subjects exhibited viral load rebound at days 16 or 28 after dosing, Dr. DeVincenzo said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

The study subjects, who had RSV-A specific antibody titers in the lowest 25th percentile of the population, were inoculated at baseline and monitored for RSV infection in nasal wash every 12 hours. At either 12 hours after infection was detected or 6 days following inoculation – whichever came first – they were randomized to receive either placebo or ALS-008176 given as a loading dose of 750 mg followed by 500-mg maintenance doses, a loading dose of 750 mg followed by 150-mg maintenance doses, or 375 mg every 12 hours for 5 days. The treatment and placebo groups were well balanced with respect to age, body mass index, sex, and viral load. Assessment of viral load, RSV symptom scores, and mucous weight were evaluated multiple times daily for 12 days, then again on days 16 and 28.

A decrease in viral load in the treatment groups occurred as early as day 0.5 after the initial dose, whereas the viral load in the placebo group increased to more than 4 logs, peaking at day 3.5 and then dropping. The most dramatic decrease in viral load was seen in the highest-dose group and was better in both groups that received a loading dose than in the treatment group that did not.

Viral load in the treatment groups became undetectable very quickly, Dr. DeVincenzo said, noting that levels remained undetectable at days 16 and 28, indicating there was no rebound after dosing was stopped.

No viral resistance mutations were noted.

Treatment with ALS-008176, which is a potent and selective inhibitor of RSV RNA-dependent RNA polymerase that is active against multiple A and B strains of RSV, was well tolerated; no clinically significant laboratory abnormalities occurred, and adverse events all were mild or moderate and were generally balanced between the placebo and treatment groups. None of the volunteers discontinued the study because of adverse events, Dr. DeVincenzo said.

The findings are encouraging given the lack of an effective treatment or vaccine for RSV, which is an important cause of morbidity and mortality worldwide – particularly in infants.

“Further studies of ALS-008176 in natural infections are warranted,” he said, noting that such studies are currently ongoing, including one in otherwise healthy infants hospitalized with RSV.

Dr. DeVincenzo is a consultant for, and/or has received research support from, Abbvie, Alios Biopharma, Alnylam, Ark Pharma, Astra Zeneca, Biota, Crucell, the Genomics Institute of the Novartis Research Foundation, Gilead Sciences, Janssen, MedImmune, Retroscreen Virology, Teva, and Novartis.

PHILADELPHIA – ALS-008176, an oral prodrug of the novel cytidine nucleoside analog, rapidly reduced respiratory syncitial virus load and clinical disease severity in healthy adult volunteers infected with a clinical strain of the virus as part of a double-blind, placebo-controlled phase IIa study.

Of 62 adults aged 18-45 years with preexisting RSV-A specific antibody titers who were inoculated with RSV-A Memphis 37b virus and randomized to receive placebo or one of three ALS-008176 dosing regimens, 35 met the criteria for infection. The viral load area under the curve (AUC) was significantly and rapidly reduced in all volunteers who received ALS-008176, compared with those who received placebo; the reduction in AUC, compared with placebo, ranged from 73% to 88% for the treatment groups at day 12 , Dr. John DeVincenzo of the University of Tennessee Health Science Center, Memphis, reported at an annual scientific meeting on infectious diseases.

Further, the AUC for symptom scores and mucous quantity as measured by weight were also reduced for all treatment groups, compared with placebo, and no subjects exhibited viral load rebound at days 16 or 28 after dosing, Dr. DeVincenzo said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

The study subjects, who had RSV-A specific antibody titers in the lowest 25th percentile of the population, were inoculated at baseline and monitored for RSV infection in nasal wash every 12 hours. At either 12 hours after infection was detected or 6 days following inoculation – whichever came first – they were randomized to receive either placebo or ALS-008176 given as a loading dose of 750 mg followed by 500-mg maintenance doses, a loading dose of 750 mg followed by 150-mg maintenance doses, or 375 mg every 12 hours for 5 days. The treatment and placebo groups were well balanced with respect to age, body mass index, sex, and viral load. Assessment of viral load, RSV symptom scores, and mucous weight were evaluated multiple times daily for 12 days, then again on days 16 and 28.

A decrease in viral load in the treatment groups occurred as early as day 0.5 after the initial dose, whereas the viral load in the placebo group increased to more than 4 logs, peaking at day 3.5 and then dropping. The most dramatic decrease in viral load was seen in the highest-dose group and was better in both groups that received a loading dose than in the treatment group that did not.

Viral load in the treatment groups became undetectable very quickly, Dr. DeVincenzo said, noting that levels remained undetectable at days 16 and 28, indicating there was no rebound after dosing was stopped.

No viral resistance mutations were noted.

Treatment with ALS-008176, which is a potent and selective inhibitor of RSV RNA-dependent RNA polymerase that is active against multiple A and B strains of RSV, was well tolerated; no clinically significant laboratory abnormalities occurred, and adverse events all were mild or moderate and were generally balanced between the placebo and treatment groups. None of the volunteers discontinued the study because of adverse events, Dr. DeVincenzo said.

The findings are encouraging given the lack of an effective treatment or vaccine for RSV, which is an important cause of morbidity and mortality worldwide – particularly in infants.

“Further studies of ALS-008176 in natural infections are warranted,” he said, noting that such studies are currently ongoing, including one in otherwise healthy infants hospitalized with RSV.

Dr. DeVincenzo is a consultant for, and/or has received research support from, Abbvie, Alios Biopharma, Alnylam, Ark Pharma, Astra Zeneca, Biota, Crucell, the Genomics Institute of the Novartis Research Foundation, Gilead Sciences, Janssen, MedImmune, Retroscreen Virology, Teva, and Novartis.

PHILADELPHIA – ALS-008176, an oral prodrug of the novel cytidine nucleoside analog, rapidly reduced respiratory syncitial virus load and clinical disease severity in healthy adult volunteers infected with a clinical strain of the virus as part of a double-blind, placebo-controlled phase IIa study.

Of 62 adults aged 18-45 years with preexisting RSV-A specific antibody titers who were inoculated with RSV-A Memphis 37b virus and randomized to receive placebo or one of three ALS-008176 dosing regimens, 35 met the criteria for infection. The viral load area under the curve (AUC) was significantly and rapidly reduced in all volunteers who received ALS-008176, compared with those who received placebo; the reduction in AUC, compared with placebo, ranged from 73% to 88% for the treatment groups at day 12 , Dr. John DeVincenzo of the University of Tennessee Health Science Center, Memphis, reported at an annual scientific meeting on infectious diseases.

Further, the AUC for symptom scores and mucous quantity as measured by weight were also reduced for all treatment groups, compared with placebo, and no subjects exhibited viral load rebound at days 16 or 28 after dosing, Dr. DeVincenzo said at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society.

The study subjects, who had RSV-A specific antibody titers in the lowest 25th percentile of the population, were inoculated at baseline and monitored for RSV infection in nasal wash every 12 hours. At either 12 hours after infection was detected or 6 days following inoculation – whichever came first – they were randomized to receive either placebo or ALS-008176 given as a loading dose of 750 mg followed by 500-mg maintenance doses, a loading dose of 750 mg followed by 150-mg maintenance doses, or 375 mg every 12 hours for 5 days. The treatment and placebo groups were well balanced with respect to age, body mass index, sex, and viral load. Assessment of viral load, RSV symptom scores, and mucous weight were evaluated multiple times daily for 12 days, then again on days 16 and 28.

A decrease in viral load in the treatment groups occurred as early as day 0.5 after the initial dose, whereas the viral load in the placebo group increased to more than 4 logs, peaking at day 3.5 and then dropping. The most dramatic decrease in viral load was seen in the highest-dose group and was better in both groups that received a loading dose than in the treatment group that did not.

Viral load in the treatment groups became undetectable very quickly, Dr. DeVincenzo said, noting that levels remained undetectable at days 16 and 28, indicating there was no rebound after dosing was stopped.

No viral resistance mutations were noted.

Treatment with ALS-008176, which is a potent and selective inhibitor of RSV RNA-dependent RNA polymerase that is active against multiple A and B strains of RSV, was well tolerated; no clinically significant laboratory abnormalities occurred, and adverse events all were mild or moderate and were generally balanced between the placebo and treatment groups. None of the volunteers discontinued the study because of adverse events, Dr. DeVincenzo said.

The findings are encouraging given the lack of an effective treatment or vaccine for RSV, which is an important cause of morbidity and mortality worldwide – particularly in infants.

“Further studies of ALS-008176 in natural infections are warranted,” he said, noting that such studies are currently ongoing, including one in otherwise healthy infants hospitalized with RSV.

Dr. DeVincenzo is a consultant for, and/or has received research support from, Abbvie, Alios Biopharma, Alnylam, Ark Pharma, Astra Zeneca, Biota, Crucell, the Genomics Institute of the Novartis Research Foundation, Gilead Sciences, Janssen, MedImmune, Retroscreen Virology, Teva, and Novartis.

AUSTIN, TEX. – Patients who consider themselves too sexy for their continuous positive airway pressure devices should reconsider, according to a presenter at the annual meeting of the American College of Chest Physicians.

“Despite the unsexy appearance of a positive airway pressure device in the bedroom, patients who don’t comply with their CPAP [protocols] do not have a better sexual quality of life,” said Dr. Salman Alim, who presented the original investigation during a quality and clinical improvement session.

Sexual quality of life questionnaires were distributed to 52 men being treated at a single site with continuous positive airway pressure (CPAP) for obstructive sleep apnea. The 10-question survey used a scale of 1-8, with 80 being the highest score, to evaluate aspects of the participants’ emotional and physical satisfaction with their sex lives. Patients were considered CPAP-compliant if they used their device 4 or more hours nightly at least 70% of the time before going to sleep.

The compliant cohort of 27 men, whose average age was 59 years, had a sexual quality of life score of about 38. The noncompliant group of 25 men, whose average age was 56 years, had a score of about 48.

After adjusting for confounding variables such as age, body mass index, erectile dysfunction, use of phosphodiesterase inhibitors, and depression, CPAP compliance did not predict one’s sexual quality of life, reported Dr. Alim, who was with Rosalind Franklin University in North Chicago, Ill., at the time of the study and is now with Physicians Regional Healthcare System in Naples, Fla.

“Although this is not a validated survey … the study’s findings can be the basis to develop a hypothesis that can be tested more rigorously. At the least, the results provide clinicians with useful information on counseling patients on adherence with CPAP,” Dr. Mark Rosen, medical director of the American College of Chest Physicians, said in an interview.

The authors of the study said that they had no relevant disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

AUSTIN, TEX. – Patients who consider themselves too sexy for their continuous positive airway pressure devices should reconsider, according to a presenter at the annual meeting of the American College of Chest Physicians.

“Despite the unsexy appearance of a positive airway pressure device in the bedroom, patients who don’t comply with their CPAP [protocols] do not have a better sexual quality of life,” said Dr. Salman Alim, who presented the original investigation during a quality and clinical improvement session.

Sexual quality of life questionnaires were distributed to 52 men being treated at a single site with continuous positive airway pressure (CPAP) for obstructive sleep apnea. The 10-question survey used a scale of 1-8, with 80 being the highest score, to evaluate aspects of the participants’ emotional and physical satisfaction with their sex lives. Patients were considered CPAP-compliant if they used their device 4 or more hours nightly at least 70% of the time before going to sleep.

The compliant cohort of 27 men, whose average age was 59 years, had a sexual quality of life score of about 38. The noncompliant group of 25 men, whose average age was 56 years, had a score of about 48.

After adjusting for confounding variables such as age, body mass index, erectile dysfunction, use of phosphodiesterase inhibitors, and depression, CPAP compliance did not predict one’s sexual quality of life, reported Dr. Alim, who was with Rosalind Franklin University in North Chicago, Ill., at the time of the study and is now with Physicians Regional Healthcare System in Naples, Fla.

“Although this is not a validated survey … the study’s findings can be the basis to develop a hypothesis that can be tested more rigorously. At the least, the results provide clinicians with useful information on counseling patients on adherence with CPAP,” Dr. Mark Rosen, medical director of the American College of Chest Physicians, said in an interview.

The authors of the study said that they had no relevant disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

AUSTIN, TEX. – Patients who consider themselves too sexy for their continuous positive airway pressure devices should reconsider, according to a presenter at the annual meeting of the American College of Chest Physicians.

“Despite the unsexy appearance of a positive airway pressure device in the bedroom, patients who don’t comply with their CPAP [protocols] do not have a better sexual quality of life,” said Dr. Salman Alim, who presented the original investigation during a quality and clinical improvement session.

Sexual quality of life questionnaires were distributed to 52 men being treated at a single site with continuous positive airway pressure (CPAP) for obstructive sleep apnea. The 10-question survey used a scale of 1-8, with 80 being the highest score, to evaluate aspects of the participants’ emotional and physical satisfaction with their sex lives. Patients were considered CPAP-compliant if they used their device 4 or more hours nightly at least 70% of the time before going to sleep.

The compliant cohort of 27 men, whose average age was 59 years, had a sexual quality of life score of about 38. The noncompliant group of 25 men, whose average age was 56 years, had a score of about 48.

After adjusting for confounding variables such as age, body mass index, erectile dysfunction, use of phosphodiesterase inhibitors, and depression, CPAP compliance did not predict one’s sexual quality of life, reported Dr. Alim, who was with Rosalind Franklin University in North Chicago, Ill., at the time of the study and is now with Physicians Regional Healthcare System in Naples, Fla.

“Although this is not a validated survey … the study’s findings can be the basis to develop a hypothesis that can be tested more rigorously. At the least, the results provide clinicians with useful information on counseling patients on adherence with CPAP,” Dr. Mark Rosen, medical director of the American College of Chest Physicians, said in an interview.

The authors of the study said that they had no relevant disclosures.

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight

The phase III trial of a tetravalent dengue vaccine among children in Latin America has shown the vaccine to be protective against the virus, with significant reductions in the risk of hospitalization with dengue.

The placebo-controlled trial of a three-dose vaccine schedule among 20,869 children living in dengue-endemic regions showed a vaccine efficacy of 60.8% in the per-protocol analysis and 64.7% in the intention-to-treat population of individuals who received at least one injection, researchers said at the annual meeting of the American Society of Tropical Medicine and Hygiene.

© World Health Organization

The vaccine had an efficacy of 95.5% in preventing severe dengue and 80.3% efficacy in preventing hospitalization, while also showing efficacy against serotypes 1, 2, 3, and 4 and a rate of adverse events similar to that of the placebo group, according to a paper published simultaneously online in the New England Journal of Medicine (2014 Nov. 3 [doi:10.1056/NEJMoa1411037]).

“Overall, the results of our study and the Asian study provide a consistent picture of the efficacy and safety of this dengue vaccine after 25 months of active surveillance in 10 countries among different populations (including a variety of ages and ethnic backgrounds) over different seasons with different circulating serotypes and levels of endemicity,” wrote Dr. Luis Villar of the Universidad Industrial de Santander, Colombia, and colleagues.

The study was supported by Sanofi Pasteur. Some authors were employees of Sanofi Pasteur, and others declared institutional and research grants and honoraria from the study sponsor and other pharmaceutical companies.

The phase III trial of a tetravalent dengue vaccine among children in Latin America has shown the vaccine to be protective against the virus, with significant reductions in the risk of hospitalization with dengue.

The placebo-controlled trial of a three-dose vaccine schedule among 20,869 children living in dengue-endemic regions showed a vaccine efficacy of 60.8% in the per-protocol analysis and 64.7% in the intention-to-treat population of individuals who received at least one injection, researchers said at the annual meeting of the American Society of Tropical Medicine and Hygiene.

© World Health Organization

The vaccine had an efficacy of 95.5% in preventing severe dengue and 80.3% efficacy in preventing hospitalization, while also showing efficacy against serotypes 1, 2, 3, and 4 and a rate of adverse events similar to that of the placebo group, according to a paper published simultaneously online in the New England Journal of Medicine (2014 Nov. 3 [doi:10.1056/NEJMoa1411037]).

“Overall, the results of our study and the Asian study provide a consistent picture of the efficacy and safety of this dengue vaccine after 25 months of active surveillance in 10 countries among different populations (including a variety of ages and ethnic backgrounds) over different seasons with different circulating serotypes and levels of endemicity,” wrote Dr. Luis Villar of the Universidad Industrial de Santander, Colombia, and colleagues.

The study was supported by Sanofi Pasteur. Some authors were employees of Sanofi Pasteur, and others declared institutional and research grants and honoraria from the study sponsor and other pharmaceutical companies.

The phase III trial of a tetravalent dengue vaccine among children in Latin America has shown the vaccine to be protective against the virus, with significant reductions in the risk of hospitalization with dengue.

The placebo-controlled trial of a three-dose vaccine schedule among 20,869 children living in dengue-endemic regions showed a vaccine efficacy of 60.8% in the per-protocol analysis and 64.7% in the intention-to-treat population of individuals who received at least one injection, researchers said at the annual meeting of the American Society of Tropical Medicine and Hygiene.

© World Health Organization

The vaccine had an efficacy of 95.5% in preventing severe dengue and 80.3% efficacy in preventing hospitalization, while also showing efficacy against serotypes 1, 2, 3, and 4 and a rate of adverse events similar to that of the placebo group, according to a paper published simultaneously online in the New England Journal of Medicine (2014 Nov. 3 [doi:10.1056/NEJMoa1411037]).

“Overall, the results of our study and the Asian study provide a consistent picture of the efficacy and safety of this dengue vaccine after 25 months of active surveillance in 10 countries among different populations (including a variety of ages and ethnic backgrounds) over different seasons with different circulating serotypes and levels of endemicity,” wrote Dr. Luis Villar of the Universidad Industrial de Santander, Colombia, and colleagues.

The study was supported by Sanofi Pasteur. Some authors were employees of Sanofi Pasteur, and others declared institutional and research grants and honoraria from the study sponsor and other pharmaceutical companies.

PHILADELPHIA – Receiving a flu shot cut the odds of influenza hospitalizations by 56% among older adults during the 2010-2011 flu season, surveillance data show.

Vaccine effectiveness was consistent across all age groups, even among those aged 75 years or older.

“Continued emphasis on the importance of influenza vaccination among older adults is crucial,” Dr. Fiona Havers said at an annual scientific meeting on infectious diseases.

She reported on 364 adults, aged 50 years and older, who received a flu shot at least 14 days prior to hospital admission for laboratory-confirmed influenza during the 2010-2011 season. Cases were admitted to one of 11 sites participating in the Emerging Infections Program, now FluSurv-Net, and were matched by age and county to 773 controls.

Cases were significantly more likely than were controls to be of nonwhite race (31% vs. 15%), to be Hispanic (7% vs. 2%), to have an annual income less than $35,000 (52% vs. 33%), to have high school or lower-level education (44% vs. 27%), and to have at least two chronic health conditions (72% vs. 36%) (P values < .01 for all).

Estimates of influenza vaccine effectiveness in preventing hospitalization was 33% for all ages, 33% for ages 50-64 years, 45% for ages 65-74 years, and 21% for those 75 years and older, reported Dr. Havers of the influenza division of the Centers for Disease Control and Prevention in Atlanta.

After adjustment for age, gender, race/ethnicity, income, education, recent hospitalization, functional status, and chronic medical conditions, vaccine effectiveness estimates were 56%, 64%, 61%, and 57%, respectively, (P values < .05 for all).

The investigators also looked at influenza subtype and found that after adjustment, vaccination was associated with a significant reduction in the risk of hospitalizations for influenza A H3N2 (51%) and influenza B (95%), but not influenza A H1N1 (46%), likely because of the small number of H1N1 cases, said Dr. Havers, who urged older adults to seek care if they develop symptoms, even if they were vaccinated.

“We know that antiviral treatment is recommended for all older adults with suspected influenza, as they are at high risk for influenza complications, and antiviral drugs work best if given promptly after symptoms develop,” she said in an interview. ID Week comprises the combined annual meetings of the Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, HIV Medicine Association, and Pediatric Infectious Diseases Society.

pwendling@frontlinemedcom.com

PHILADELPHIA – Receiving a flu shot cut the odds of influenza hospitalizations by 56% among older adults during the 2010-2011 flu season, surveillance data show.

Vaccine effectiveness was consistent across all age groups, even among those aged 75 years or older.

“Continued emphasis on the importance of influenza vaccination among older adults is crucial,” Dr. Fiona Havers said at an annual scientific meeting on infectious diseases.

She reported on 364 adults, aged 50 years and older, who received a flu shot at least 14 days prior to hospital admission for laboratory-confirmed influenza during the 2010-2011 season. Cases were admitted to one of 11 sites participating in the Emerging Infections Program, now FluSurv-Net, and were matched by age and county to 773 controls.

Cases were significantly more likely than were controls to be of nonwhite race (31% vs. 15%), to be Hispanic (7% vs. 2%), to have an annual income less than $35,000 (52% vs. 33%), to have high school or lower-level education (44% vs. 27%), and to have at least two chronic health conditions (72% vs. 36%) (P values < .01 for all).

Estimates of influenza vaccine effectiveness in preventing hospitalization was 33% for all ages, 33% for ages 50-64 years, 45% for ages 65-74 years, and 21% for those 75 years and older, reported Dr. Havers of the influenza division of the Centers for Disease Control and Prevention in Atlanta.

After adjustment for age, gender, race/ethnicity, income, education, recent hospitalization, functional status, and chronic medical conditions, vaccine effectiveness estimates were 56%, 64%, 61%, and 57%, respectively, (P values < .05 for all).

The investigators also looked at influenza subtype and found that after adjustment, vaccination was associated with a significant reduction in the risk of hospitalizations for influenza A H3N2 (51%) and influenza B (95%), but not influenza A H1N1 (46%), likely because of the small number of H1N1 cases, said Dr. Havers, who urged older adults to seek care if they develop symptoms, even if they were vaccinated.

“We know that antiviral treatment is recommended for all older adults with suspected influenza, as they are at high risk for influenza complications, and antiviral drugs work best if given promptly after symptoms develop,” she said in an interview. ID Week comprises the combined annual meetings of the Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, HIV Medicine Association, and Pediatric Infectious Diseases Society.

pwendling@frontlinemedcom.com

PHILADELPHIA – Receiving a flu shot cut the odds of influenza hospitalizations by 56% among older adults during the 2010-2011 flu season, surveillance data show.

Vaccine effectiveness was consistent across all age groups, even among those aged 75 years or older.

“Continued emphasis on the importance of influenza vaccination among older adults is crucial,” Dr. Fiona Havers said at an annual scientific meeting on infectious diseases.

She reported on 364 adults, aged 50 years and older, who received a flu shot at least 14 days prior to hospital admission for laboratory-confirmed influenza during the 2010-2011 season. Cases were admitted to one of 11 sites participating in the Emerging Infections Program, now FluSurv-Net, and were matched by age and county to 773 controls.

Cases were significantly more likely than were controls to be of nonwhite race (31% vs. 15%), to be Hispanic (7% vs. 2%), to have an annual income less than $35,000 (52% vs. 33%), to have high school or lower-level education (44% vs. 27%), and to have at least two chronic health conditions (72% vs. 36%) (P values < .01 for all).

Estimates of influenza vaccine effectiveness in preventing hospitalization was 33% for all ages, 33% for ages 50-64 years, 45% for ages 65-74 years, and 21% for those 75 years and older, reported Dr. Havers of the influenza division of the Centers for Disease Control and Prevention in Atlanta.

After adjustment for age, gender, race/ethnicity, income, education, recent hospitalization, functional status, and chronic medical conditions, vaccine effectiveness estimates were 56%, 64%, 61%, and 57%, respectively, (P values < .05 for all).

The investigators also looked at influenza subtype and found that after adjustment, vaccination was associated with a significant reduction in the risk of hospitalizations for influenza A H3N2 (51%) and influenza B (95%), but not influenza A H1N1 (46%), likely because of the small number of H1N1 cases, said Dr. Havers, who urged older adults to seek care if they develop symptoms, even if they were vaccinated.

“We know that antiviral treatment is recommended for all older adults with suspected influenza, as they are at high risk for influenza complications, and antiviral drugs work best if given promptly after symptoms develop,” she said in an interview. ID Week comprises the combined annual meetings of the Infectious Diseases Society of America, Society for Healthcare Epidemiology of America, HIV Medicine Association, and Pediatric Infectious Diseases Society.

pwendling@frontlinemedcom.com

VANCOUVER, B.C. – The “shotgun” style of skin prick testing in children and adolescents with suspected IgE-mediated food allergy shows sensitization, but not necessarily allergy, according to Dr. James Bergman.

A positive skin test measures the presence of a specific IgE antibody, which does not necessarily equate to an allergy. Consequently, children may have multiple positive skin prick tests yet clinically tolerate the tested food, he said. “Sensitization is just the presence of a specific IgE to a food. Allergy is sensitization plus signs or symptoms upon exposure to the food.”

Dr. Bergman, who also holds a faculty position in the department of dermatology and skin science at the University of British Columbia, said the practice of shotgun skin prick testing can lead to unnecessary avoidance of specific foods. One group of researchers conducted oral food challenge tests in 125 children aged 1-9 years with a diagnosis of food allergy based on IgE tests. Nearly all of them (93%) had no reactivity when challenged with the suspect food (J. Peds. 2011; 158[4]:578-83). “Ninety-three percent of the children would have been avoiding their ‘allergic foods’ perhaps indefinitely,” said Dr. Bergman, who was not involved with the study.

“The general rule is, if you’re not having clinical symptoms that suggest an IgE-mediated reaction, then don’t test,” Dr. Bergman, a dermatologist who practices in Vancouver, said at the annual meeting of the Pacific Dermatologic Association.

“I explain to parents that if they want to test for a food in the situation where there is no IgE-mediated reaction, then it can be done, but there is a significant risk of a false positive or ‘fake allergy,’ ” he said. “In this situation the only way of knowing for sure whether it is an allergy is to undertake a formal oral food challenge, which is the (highest) standard for diagnosing food allergy.”

Telltale symptoms of an IgE-mediated food allergy include hives, vomiting, diarrhea, breathing problems, and change in level of consciousness. “These symptoms typically occur within minutes of ingestion, sometimes within 30 minutes and rarely up to 2 hours,” Dr. Bergman said. “If it’s beyond 2 hours, it’s unlikely to be IgE mediated.”

“If someone has a true food allergy, advise them to avoid the culprit food, give them an epinephrine injector, and refer them to an allergist for testing, education, and follow-up,” he advised.

Food allergies affect 6%-8% of pediatric patients, yet 35%- 90% of families self-report food allergies depending on the population studied. Milk, egg, wheat, peanuts, nuts, soy, and seafood account for 90% of food allergens. Most children outgrow allergy to milk, egg, wheat, and soy, while few outgrow allergy to peanuts, nuts, fish, and shellfish.

Most patients and many physicians believe that eczema is caused by food allergies. In fact, only a small minority of patients have food allergies that directly cause eczema. “Eczema could occur secondary to scratching induced by an urticarial food reaction or by a primary irritant reaction, but food directly causing isolated eczema is rare,” Dr. Bergman said. “The belief that food allergies directly cause eczema is completely understandable given that eczema patients do have an increased rate of allergies, the cyclic pattern of eczema, and the parent’s desire to find a cause for the child’s rash. Eczema’s cyclic nature can easily lead to a specific food being implicated due to recall bias. The parent will remember the flares that occurred with exposure to the specific food, while not recalling the times when the food was tolerated or the flares that were not associated with the food.”

If a parent is worried about a food causing eczema and there are no IgE mediated symptoms, then instead of testing he will often recommend that the family keep a formal food symptom diary while they are intermittently ingesting the food of concern. “The vast majority of parents will see no consistent direct correlation with the food and they can feel comfortable with ongoing future ingestion,” he said.

Some clinicians are offering oral immune therapy to patients with IgE-mediated food allergy. Dr. Bergman characterized such practice as “risky” at this point in time. “It’s like the traditional allergy shots you’d get for your pollen allergy, except it’s done orally,” he explained. “Research is being done in this area by introducing small amounts [of the allergen], in an attempt to induce tolerance. The results are encouraging, but the problem is that patients can have bad reactions. We also don’t know how well or for how long it will work. At this point, while promising, the field is not yet ready for prime time.”

He also said there is no current evidence supporting IgG testing, Vega testing, or muscle strength testing in the investigation of suspected IgE-mediated food allergy. “What I tell patients is that if any of these tests identifies something, it probably identifies something that’s mild and very temporary, because in my experience patients with positive IgG tests are usually told to avoid the food for 1-4 months and then to reintroduce that food in a rotation basis. Avoidance of food allergens based on this type of testing is not necessary. However, for patients who still wish to practice short term avoidance of the food then this is fine provided the diet does not compromise nutrition.”

Dr. Bergman reported having no financial disclosures.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

VANCOUVER, B.C. – The “shotgun” style of skin prick testing in children and adolescents with suspected IgE-mediated food allergy shows sensitization, but not necessarily allergy, according to Dr. James Bergman.

A positive skin test measures the presence of a specific IgE antibody, which does not necessarily equate to an allergy. Consequently, children may have multiple positive skin prick tests yet clinically tolerate the tested food, he said. “Sensitization is just the presence of a specific IgE to a food. Allergy is sensitization plus signs or symptoms upon exposure to the food.”

Dr. Bergman, who also holds a faculty position in the department of dermatology and skin science at the University of British Columbia, said the practice of shotgun skin prick testing can lead to unnecessary avoidance of specific foods. One group of researchers conducted oral food challenge tests in 125 children aged 1-9 years with a diagnosis of food allergy based on IgE tests. Nearly all of them (93%) had no reactivity when challenged with the suspect food (J. Peds. 2011; 158[4]:578-83). “Ninety-three percent of the children would have been avoiding their ‘allergic foods’ perhaps indefinitely,” said Dr. Bergman, who was not involved with the study.

“The general rule is, if you’re not having clinical symptoms that suggest an IgE-mediated reaction, then don’t test,” Dr. Bergman, a dermatologist who practices in Vancouver, said at the annual meeting of the Pacific Dermatologic Association.

“I explain to parents that if they want to test for a food in the situation where there is no IgE-mediated reaction, then it can be done, but there is a significant risk of a false positive or ‘fake allergy,’ ” he said. “In this situation the only way of knowing for sure whether it is an allergy is to undertake a formal oral food challenge, which is the (highest) standard for diagnosing food allergy.”

Telltale symptoms of an IgE-mediated food allergy include hives, vomiting, diarrhea, breathing problems, and change in level of consciousness. “These symptoms typically occur within minutes of ingestion, sometimes within 30 minutes and rarely up to 2 hours,” Dr. Bergman said. “If it’s beyond 2 hours, it’s unlikely to be IgE mediated.”

“If someone has a true food allergy, advise them to avoid the culprit food, give them an epinephrine injector, and refer them to an allergist for testing, education, and follow-up,” he advised.

Food allergies affect 6%-8% of pediatric patients, yet 35%- 90% of families self-report food allergies depending on the population studied. Milk, egg, wheat, peanuts, nuts, soy, and seafood account for 90% of food allergens. Most children outgrow allergy to milk, egg, wheat, and soy, while few outgrow allergy to peanuts, nuts, fish, and shellfish.

Most patients and many physicians believe that eczema is caused by food allergies. In fact, only a small minority of patients have food allergies that directly cause eczema. “Eczema could occur secondary to scratching induced by an urticarial food reaction or by a primary irritant reaction, but food directly causing isolated eczema is rare,” Dr. Bergman said. “The belief that food allergies directly cause eczema is completely understandable given that eczema patients do have an increased rate of allergies, the cyclic pattern of eczema, and the parent’s desire to find a cause for the child’s rash. Eczema’s cyclic nature can easily lead to a specific food being implicated due to recall bias. The parent will remember the flares that occurred with exposure to the specific food, while not recalling the times when the food was tolerated or the flares that were not associated with the food.”

If a parent is worried about a food causing eczema and there are no IgE mediated symptoms, then instead of testing he will often recommend that the family keep a formal food symptom diary while they are intermittently ingesting the food of concern. “The vast majority of parents will see no consistent direct correlation with the food and they can feel comfortable with ongoing future ingestion,” he said.

Some clinicians are offering oral immune therapy to patients with IgE-mediated food allergy. Dr. Bergman characterized such practice as “risky” at this point in time. “It’s like the traditional allergy shots you’d get for your pollen allergy, except it’s done orally,” he explained. “Research is being done in this area by introducing small amounts [of the allergen], in an attempt to induce tolerance. The results are encouraging, but the problem is that patients can have bad reactions. We also don’t know how well or for how long it will work. At this point, while promising, the field is not yet ready for prime time.”

He also said there is no current evidence supporting IgG testing, Vega testing, or muscle strength testing in the investigation of suspected IgE-mediated food allergy. “What I tell patients is that if any of these tests identifies something, it probably identifies something that’s mild and very temporary, because in my experience patients with positive IgG tests are usually told to avoid the food for 1-4 months and then to reintroduce that food in a rotation basis. Avoidance of food allergens based on this type of testing is not necessary. However, for patients who still wish to practice short term avoidance of the food then this is fine provided the diet does not compromise nutrition.”

Dr. Bergman reported having no financial disclosures.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

VANCOUVER, B.C. – The “shotgun” style of skin prick testing in children and adolescents with suspected IgE-mediated food allergy shows sensitization, but not necessarily allergy, according to Dr. James Bergman.

A positive skin test measures the presence of a specific IgE antibody, which does not necessarily equate to an allergy. Consequently, children may have multiple positive skin prick tests yet clinically tolerate the tested food, he said. “Sensitization is just the presence of a specific IgE to a food. Allergy is sensitization plus signs or symptoms upon exposure to the food.”

Dr. Bergman, who also holds a faculty position in the department of dermatology and skin science at the University of British Columbia, said the practice of shotgun skin prick testing can lead to unnecessary avoidance of specific foods. One group of researchers conducted oral food challenge tests in 125 children aged 1-9 years with a diagnosis of food allergy based on IgE tests. Nearly all of them (93%) had no reactivity when challenged with the suspect food (J. Peds. 2011; 158[4]:578-83). “Ninety-three percent of the children would have been avoiding their ‘allergic foods’ perhaps indefinitely,” said Dr. Bergman, who was not involved with the study.

“The general rule is, if you’re not having clinical symptoms that suggest an IgE-mediated reaction, then don’t test,” Dr. Bergman, a dermatologist who practices in Vancouver, said at the annual meeting of the Pacific Dermatologic Association.

“I explain to parents that if they want to test for a food in the situation where there is no IgE-mediated reaction, then it can be done, but there is a significant risk of a false positive or ‘fake allergy,’ ” he said. “In this situation the only way of knowing for sure whether it is an allergy is to undertake a formal oral food challenge, which is the (highest) standard for diagnosing food allergy.”

Telltale symptoms of an IgE-mediated food allergy include hives, vomiting, diarrhea, breathing problems, and change in level of consciousness. “These symptoms typically occur within minutes of ingestion, sometimes within 30 minutes and rarely up to 2 hours,” Dr. Bergman said. “If it’s beyond 2 hours, it’s unlikely to be IgE mediated.”

“If someone has a true food allergy, advise them to avoid the culprit food, give them an epinephrine injector, and refer them to an allergist for testing, education, and follow-up,” he advised.

Food allergies affect 6%-8% of pediatric patients, yet 35%- 90% of families self-report food allergies depending on the population studied. Milk, egg, wheat, peanuts, nuts, soy, and seafood account for 90% of food allergens. Most children outgrow allergy to milk, egg, wheat, and soy, while few outgrow allergy to peanuts, nuts, fish, and shellfish.

Most patients and many physicians believe that eczema is caused by food allergies. In fact, only a small minority of patients have food allergies that directly cause eczema. “Eczema could occur secondary to scratching induced by an urticarial food reaction or by a primary irritant reaction, but food directly causing isolated eczema is rare,” Dr. Bergman said. “The belief that food allergies directly cause eczema is completely understandable given that eczema patients do have an increased rate of allergies, the cyclic pattern of eczema, and the parent’s desire to find a cause for the child’s rash. Eczema’s cyclic nature can easily lead to a specific food being implicated due to recall bias. The parent will remember the flares that occurred with exposure to the specific food, while not recalling the times when the food was tolerated or the flares that were not associated with the food.”

If a parent is worried about a food causing eczema and there are no IgE mediated symptoms, then instead of testing he will often recommend that the family keep a formal food symptom diary while they are intermittently ingesting the food of concern. “The vast majority of parents will see no consistent direct correlation with the food and they can feel comfortable with ongoing future ingestion,” he said.

Some clinicians are offering oral immune therapy to patients with IgE-mediated food allergy. Dr. Bergman characterized such practice as “risky” at this point in time. “It’s like the traditional allergy shots you’d get for your pollen allergy, except it’s done orally,” he explained. “Research is being done in this area by introducing small amounts [of the allergen], in an attempt to induce tolerance. The results are encouraging, but the problem is that patients can have bad reactions. We also don’t know how well or for how long it will work. At this point, while promising, the field is not yet ready for prime time.”

He also said there is no current evidence supporting IgG testing, Vega testing, or muscle strength testing in the investigation of suspected IgE-mediated food allergy. “What I tell patients is that if any of these tests identifies something, it probably identifies something that’s mild and very temporary, because in my experience patients with positive IgG tests are usually told to avoid the food for 1-4 months and then to reintroduce that food in a rotation basis. Avoidance of food allergens based on this type of testing is not necessary. However, for patients who still wish to practice short term avoidance of the food then this is fine provided the diet does not compromise nutrition.”

Dr. Bergman reported having no financial disclosures.

dbrunk@frontlinemedcom.com

On Twitter @dougbrunk

SAN DIEGO – Children who parents describe as “always sick” often are immunologically normal, but knowing when to suspect otherwise is crucial, according to Dr. Meg Fisher.

“When parents tell you their child is sick all the time, they are. They’re literally just recovering from one thing when they pick up the next,” said Dr. Fisher, a pediatric infectious diseases specialist at Monmouth Medical Center in West Orange, N.J.

CDC/Janice Haney Carr

Children under 2 years of age typically acquire 4-10 symptomatic respiratory infections per year – and up to 13 if they are in day care, Dr. Fisher said. These children also normally develop one to four gastrointestinal infections per year, she added. And children older than 2 years average four to eight respiratory infections and up to two gastrointestinal infections annually, she said at the annual meeting of the American Academy of Pediatrics .

Certain types of infections always merit a closer look, Dr. Fisher emphasized. Invasive infections, recurrent meningitis, excessive episodes of respiratory disease, chronic diarrhea, recurrent urinary tract infections, and recurrent skin and soft tissue infections can indicate immunodeficient disorders, inherited diseases such as cystic fibrosis, or anatomic abnormalities that predispose children to serious infections, she said. “The site of recurrent infections is really going to help you determine which subspecialist you need,” she added.

Culture results also provide clues about underlying conditions. “If you ever recover Pseudomonas aeruginosa from the respiratory tract of a child, you should automatically think about cystic fibrosis,” Dr. Fisher said. Pseudomonas is often isolated from stool samples, but is not normally found in a child’s respiratory tract, she explained.

“Unusual organisms and abnormal laboratory results should always trigger a follow-up evaluation,” Dr. Stuart Abramson said in a related presentation. The most common primary immunodeficiency disorders include selective IgA deficiency – which affects 1 in 500 children – IgG₂deficiency, transient hypogammaglobulinemia of infancy, and DiGeorge anomaly, said Dr. Abramson, who is director of allergy and immunology services at Shannon Medical Center in San Angelo, Tex. Less common primary immunodeficiencies affect 1 in 50,000 to 1 in 200,000 children and include B-cell disorders, T-cell disorders, phagocytic disorders, and complement disorders, he said at the meeting.

Of the four stages of testing for primary immunodeficiencies, only the first stage needs to be done by the primary care pediatrician; testing at the first stage includes taking a history and physical examination, complete blood count and differential, and quantitative immunoglobulin levels for IgA, IgG, and IgM, said Dr. Fisher. A child who needs further testing “might be better served by an immunologist,” she added.

Pediatricians should consider first-stage testing if a patient presents with one or more warning signs of a primary immunodeficiency in children, Dr. Abramson said.

Those warning signs are:

• Four or more new ear infections within 1 year.

• Two or more serious sinus infections within 1 year.

• Two or more months on antibiotics with little effect.

• Two or more pneumonias within 1 year.

• Failure of an infant to gain weight or grow normally.

• Recurrent, deep abscesses of the skin or organs.

• Persistent oral thrush or cutaneous mycoses.

• Need for intravenous antibiotics to clear infections.

• Two or more deep-seated infections, including septicemia.

• A family history of primary immunodeficiency.

(This list was assembled by the Jeffrey Modell Foundation.)

Dr. Fisher and Dr. Abramson declared no relevant financial relationships.

SAN DIEGO – Children who parents describe as “always sick” often are immunologically normal, but knowing when to suspect otherwise is crucial, according to Dr. Meg Fisher.

“When parents tell you their child is sick all the time, they are. They’re literally just recovering from one thing when they pick up the next,” said Dr. Fisher, a pediatric infectious diseases specialist at Monmouth Medical Center in West Orange, N.J.

CDC/Janice Haney Carr

Children under 2 years of age typically acquire 4-10 symptomatic respiratory infections per year – and up to 13 if they are in day care, Dr. Fisher said. These children also normally develop one to four gastrointestinal infections per year, she added. And children older than 2 years average four to eight respiratory infections and up to two gastrointestinal infections annually, she said at the annual meeting of the American Academy of Pediatrics .

Certain types of infections always merit a closer look, Dr. Fisher emphasized. Invasive infections, recurrent meningitis, excessive episodes of respiratory disease, chronic diarrhea, recurrent urinary tract infections, and recurrent skin and soft tissue infections can indicate immunodeficient disorders, inherited diseases such as cystic fibrosis, or anatomic abnormalities that predispose children to serious infections, she said. “The site of recurrent infections is really going to help you determine which subspecialist you need,” she added.

Culture results also provide clues about underlying conditions. “If you ever recover Pseudomonas aeruginosa from the respiratory tract of a child, you should automatically think about cystic fibrosis,” Dr. Fisher said. Pseudomonas is often isolated from stool samples, but is not normally found in a child’s respiratory tract, she explained.

“Unusual organisms and abnormal laboratory results should always trigger a follow-up evaluation,” Dr. Stuart Abramson said in a related presentation. The most common primary immunodeficiency disorders include selective IgA deficiency – which affects 1 in 500 children – IgG₂deficiency, transient hypogammaglobulinemia of infancy, and DiGeorge anomaly, said Dr. Abramson, who is director of allergy and immunology services at Shannon Medical Center in San Angelo, Tex. Less common primary immunodeficiencies affect 1 in 50,000 to 1 in 200,000 children and include B-cell disorders, T-cell disorders, phagocytic disorders, and complement disorders, he said at the meeting.

Of the four stages of testing for primary immunodeficiencies, only the first stage needs to be done by the primary care pediatrician; testing at the first stage includes taking a history and physical examination, complete blood count and differential, and quantitative immunoglobulin levels for IgA, IgG, and IgM, said Dr. Fisher. A child who needs further testing “might be better served by an immunologist,” she added.

Pediatricians should consider first-stage testing if a patient presents with one or more warning signs of a primary immunodeficiency in children, Dr. Abramson said.

Those warning signs are:

• Four or more new ear infections within 1 year.

• Two or more serious sinus infections within 1 year.

• Two or more months on antibiotics with little effect.

• Two or more pneumonias within 1 year.

• Failure of an infant to gain weight or grow normally.

• Recurrent, deep abscesses of the skin or organs.

• Persistent oral thrush or cutaneous mycoses.

• Need for intravenous antibiotics to clear infections.

• Two or more deep-seated infections, including septicemia.

• A family history of primary immunodeficiency.

(This list was assembled by the Jeffrey Modell Foundation.)

Dr. Fisher and Dr. Abramson declared no relevant financial relationships.

SAN DIEGO – Children who parents describe as “always sick” often are immunologically normal, but knowing when to suspect otherwise is crucial, according to Dr. Meg Fisher.

“When parents tell you their child is sick all the time, they are. They’re literally just recovering from one thing when they pick up the next,” said Dr. Fisher, a pediatric infectious diseases specialist at Monmouth Medical Center in West Orange, N.J.

CDC/Janice Haney Carr

Children under 2 years of age typically acquire 4-10 symptomatic respiratory infections per year – and up to 13 if they are in day care, Dr. Fisher said. These children also normally develop one to four gastrointestinal infections per year, she added. And children older than 2 years average four to eight respiratory infections and up to two gastrointestinal infections annually, she said at the annual meeting of the American Academy of Pediatrics .

Certain types of infections always merit a closer look, Dr. Fisher emphasized. Invasive infections, recurrent meningitis, excessive episodes of respiratory disease, chronic diarrhea, recurrent urinary tract infections, and recurrent skin and soft tissue infections can indicate immunodeficient disorders, inherited diseases such as cystic fibrosis, or anatomic abnormalities that predispose children to serious infections, she said. “The site of recurrent infections is really going to help you determine which subspecialist you need,” she added.

Culture results also provide clues about underlying conditions. “If you ever recover Pseudomonas aeruginosa from the respiratory tract of a child, you should automatically think about cystic fibrosis,” Dr. Fisher said. Pseudomonas is often isolated from stool samples, but is not normally found in a child’s respiratory tract, she explained.

“Unusual organisms and abnormal laboratory results should always trigger a follow-up evaluation,” Dr. Stuart Abramson said in a related presentation. The most common primary immunodeficiency disorders include selective IgA deficiency – which affects 1 in 500 children – IgG₂deficiency, transient hypogammaglobulinemia of infancy, and DiGeorge anomaly, said Dr. Abramson, who is director of allergy and immunology services at Shannon Medical Center in San Angelo, Tex. Less common primary immunodeficiencies affect 1 in 50,000 to 1 in 200,000 children and include B-cell disorders, T-cell disorders, phagocytic disorders, and complement disorders, he said at the meeting.

Of the four stages of testing for primary immunodeficiencies, only the first stage needs to be done by the primary care pediatrician; testing at the first stage includes taking a history and physical examination, complete blood count and differential, and quantitative immunoglobulin levels for IgA, IgG, and IgM, said Dr. Fisher. A child who needs further testing “might be better served by an immunologist,” she added.

Pediatricians should consider first-stage testing if a patient presents with one or more warning signs of a primary immunodeficiency in children, Dr. Abramson said.

Those warning signs are:

• Four or more new ear infections within 1 year.

• Two or more serious sinus infections within 1 year.

• Two or more months on antibiotics with little effect.

• Two or more pneumonias within 1 year.

• Failure of an infant to gain weight or grow normally.

• Recurrent, deep abscesses of the skin or organs.

• Persistent oral thrush or cutaneous mycoses.

• Need for intravenous antibiotics to clear infections.

• Two or more deep-seated infections, including septicemia.

• A family history of primary immunodeficiency.

(This list was assembled by the Jeffrey Modell Foundation.)

Dr. Fisher and Dr. Abramson declared no relevant financial relationships.

AUSTIN, TEX. – Any association between opioid use and death in patients with sleep apnea cannot be explained by sleep apnea alone, according to a retrospective analysis of data from the prospective observational DREAM study.

In 1,867 patients with moderate or severe sleep apnea who were on an opioid medication, no association was seen between opioid use and severity of sleep-disordered breathing, even with increasing doses, Dr. Husham Sharifi reported at the annual meeting of the American College of Chest Physicians.

Further, when opioid use was analyzed as an unadjusted variable, it was associated with an increase in mortality (odds ratio, 1.53), but this effect was attenuated by adjustment for sleep apnea (OR, 1.52), and was further attenuated – to the point where it was no longer statistically significant – by adjustment for both sleep apnea and Charlson Comorbidity Index (OR, 1.37), said Dr. Sharifi, who was an attending physician at Brigham and Women’s Hospital, Boston, at the time he completed this research. He is now a fellow at Stanford (Calif.) University.

Sleep apnea remained an independent predictor of mortality even after adjustment for opioid use and Charlson Comorbidity Index, he said.

The DREAM study, which stands for Determining Risk of Vascular Events by Apnea Monitoring, includes a well-defined cohort of patients at three Veterans Administration sleep centers who were referred for overnight polysomnography for suspected sleep-disordered breathing between Jan. 1, 2000, and Dec. 31, 2004. All patients had an Apnea-Hypopnea Index score greater than 15, indicating moderate to severe sleep apnea, and all were on opioid medication. The patients were followed for between 3 and 10 years, with follow-up ending Dec. 31, 2010.

Opioid use has increased dramatically over the past 20 years – by more than 700%, Dr. Sharifi said.

While there does not appear to be a significant impact of opioid use on daytime respiration, there are some limited data suggesting that it may be associated with sleep-disordered breathing, he said.

The current findings, though limited by a number of factors including the observational nature of the study and possible selection bias as the DREAM cohort is a referral population, suggest that the relationship between opioid use and sleep apnea death is likely explained not by sleep apnea, but by an increased prevalence of known risk factors for morbidity and mortality in patients who take opioids and have sleep apnea, he concluded.

Dr. Sharifi reported having no disclosures.

AUSTIN, TEX. – Any association between opioid use and death in patients with sleep apnea cannot be explained by sleep apnea alone, according to a retrospective analysis of data from the prospective observational DREAM study.

In 1,867 patients with moderate or severe sleep apnea who were on an opioid medication, no association was seen between opioid use and severity of sleep-disordered breathing, even with increasing doses, Dr. Husham Sharifi reported at the annual meeting of the American College of Chest Physicians.

Further, when opioid use was analyzed as an unadjusted variable, it was associated with an increase in mortality (odds ratio, 1.53), but this effect was attenuated by adjustment for sleep apnea (OR, 1.52), and was further attenuated – to the point where it was no longer statistically significant – by adjustment for both sleep apnea and Charlson Comorbidity Index (OR, 1.37), said Dr. Sharifi, who was an attending physician at Brigham and Women’s Hospital, Boston, at the time he completed this research. He is now a fellow at Stanford (Calif.) University.

Sleep apnea remained an independent predictor of mortality even after adjustment for opioid use and Charlson Comorbidity Index, he said.

The DREAM study, which stands for Determining Risk of Vascular Events by Apnea Monitoring, includes a well-defined cohort of patients at three Veterans Administration sleep centers who were referred for overnight polysomnography for suspected sleep-disordered breathing between Jan. 1, 2000, and Dec. 31, 2004. All patients had an Apnea-Hypopnea Index score greater than 15, indicating moderate to severe sleep apnea, and all were on opioid medication. The patients were followed for between 3 and 10 years, with follow-up ending Dec. 31, 2010.

Opioid use has increased dramatically over the past 20 years – by more than 700%, Dr. Sharifi said.

While there does not appear to be a significant impact of opioid use on daytime respiration, there are some limited data suggesting that it may be associated with sleep-disordered breathing, he said.

The current findings, though limited by a number of factors including the observational nature of the study and possible selection bias as the DREAM cohort is a referral population, suggest that the relationship between opioid use and sleep apnea death is likely explained not by sleep apnea, but by an increased prevalence of known risk factors for morbidity and mortality in patients who take opioids and have sleep apnea, he concluded.

Dr. Sharifi reported having no disclosures.

AUSTIN, TEX. – Any association between opioid use and death in patients with sleep apnea cannot be explained by sleep apnea alone, according to a retrospective analysis of data from the prospective observational DREAM study.

In 1,867 patients with moderate or severe sleep apnea who were on an opioid medication, no association was seen between opioid use and severity of sleep-disordered breathing, even with increasing doses, Dr. Husham Sharifi reported at the annual meeting of the American College of Chest Physicians.

Further, when opioid use was analyzed as an unadjusted variable, it was associated with an increase in mortality (odds ratio, 1.53), but this effect was attenuated by adjustment for sleep apnea (OR, 1.52), and was further attenuated – to the point where it was no longer statistically significant – by adjustment for both sleep apnea and Charlson Comorbidity Index (OR, 1.37), said Dr. Sharifi, who was an attending physician at Brigham and Women’s Hospital, Boston, at the time he completed this research. He is now a fellow at Stanford (Calif.) University.

Sleep apnea remained an independent predictor of mortality even after adjustment for opioid use and Charlson Comorbidity Index, he said.

The DREAM study, which stands for Determining Risk of Vascular Events by Apnea Monitoring, includes a well-defined cohort of patients at three Veterans Administration sleep centers who were referred for overnight polysomnography for suspected sleep-disordered breathing between Jan. 1, 2000, and Dec. 31, 2004. All patients had an Apnea-Hypopnea Index score greater than 15, indicating moderate to severe sleep apnea, and all were on opioid medication. The patients were followed for between 3 and 10 years, with follow-up ending Dec. 31, 2010.

Opioid use has increased dramatically over the past 20 years – by more than 700%, Dr. Sharifi said.

While there does not appear to be a significant impact of opioid use on daytime respiration, there are some limited data suggesting that it may be associated with sleep-disordered breathing, he said.

The current findings, though limited by a number of factors including the observational nature of the study and possible selection bias as the DREAM cohort is a referral population, suggest that the relationship between opioid use and sleep apnea death is likely explained not by sleep apnea, but by an increased prevalence of known risk factors for morbidity and mortality in patients who take opioids and have sleep apnea, he concluded.

Dr. Sharifi reported having no disclosures.