bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Review of Evidence Supporting the American Academy of Pediatrics Recommendation for Prescribing Cephalosporin Antibiotics for Penicillin-Allergic Patients
Authors: Gern James E. 
Published: September 2006

Purpose of the Study.
The American Academy of Pediatrics, in their evidence-based guidelines for treatment of otitis media and sinusitis, endorse the use of cephalosporin antibiotics for patients with reported allergies to penicillin. Many physicians, however, remain reluctant to prescribe such agents. This article reviews evidence in support of the American Academy of Pediatrics recommendations for administration of cephalosporins to penicillin-allergic children.

Study Population and Methods.
The author reviewed data from published studies related to penicillin and cephalosporin allergies in children and adults and in animal models.

Results.
Included in this review is an examination of the types and incidence of reactions to penicillins and cephalosporins, the frequency of cross-reactivity between these 2 groups of agents, and a thorough discussion of the clinical guidelines related to penicillin and cephalosporin allergy. Experimental and clinical studies that suggest that side chain–specific antibodies predominate in the immune response to cephalosporins, thereby explaining the lack of cross-sensitivity between most cephalosporins and penicillins. Specific recommendations for the treatment of patients on the basis of their responses to previously prescribed agents are summarized.

Conclusions.
The author concludes that there is a low but measurable (0.5%) attributable risk associated with administration of a first-generation or selected second-generation cephalosporin to a patient with penicillin allergy. This increased risk is not present for third- or fourth-generation cephalosporins or for second-generation molecules with non–cross-reactive side chains.

Reviewer Comments.
This is a very careful, comprehensive, and clinically useful review article. I recommend this article to physicians who would like to understand the evidence base and immunologic concepts underlying the use of cephalosporins in penicillin-allergic individuals.
A Multisite Randomized Trial of the Effects of Physician Education and Organizational Change in Chronic Asthma Care: Cost-effectiveness Analysis of the Pediatric Asthma Care Patient Outcomes Research Team II (PAC-PORT II)
Authors: Smart Brian A. 
Published: September 2006

Purpose of the Study.
To estimate the cost-effectiveness of 2 different asthma care interventions: a peer leader–based physician behavior-change intervention (PLE) and a practice-based redesign called the planned asthma care intervention (PACI).

Study Population.
Participants were 638 children (aged 3–17 years) with mild-to-moderate asthma. More than half of the subjects were on maintenance medication.

Methods.
This was a 3-arm cluster-randomized trial conducted in 42 primary care practices. These practices were randomly assigned to PLE (n = 226), PACI (n = 213), or usual care (n = 199). The PLE strategy involved training a pediatrician at each of the practice sites as an asthma expert and champion. This leader provided support, education, and feedback to the other members of the practice with regard to asthma management. The PACI strategy included all the components of the PLE arm and also included scheduled asthma care visits with an asthma nurse, who provided standardized assessments, care planning, coordination with the primary care physician, and self-management tools. Practices in the usual-care arm received copies of the National Asthma Education and Prevention Program Expert Panel Report 2 and patient-information handouts 12 months into the study. The subjects were followed for 2 years. The primary outcome was symptom-free days (SFDs). Costs included asthma-related health care utilization and intervention.

Results.
Patients in the usual-care arm of the study had in increase in SFDs of 14.8 per year. Patients in the PLE and PACI arms had an additional gain of 6.5 and 13.3 SFDs per year, respectively, compared with the usual-care arm. When the costs of development were excluded, the cost for SFDs gained compared with usual care was $18 for PLE and $68 for PACI.

Conclusions.
It is possible to increase SFDs in children and to move organizations toward guideline recommendations for asthma management. However, the improvements were associated with an increase in the costs associated with asthma care.

Reviewer Comments.
This trial was designed to provide cost analyses to both health care providers and health maintenance organizations. It is difficult, however, to establish a threshold for cost-effectiveness. The authors cite other trials to provide a context for this question. For example, the cost-effectiveness of inhaled corticosteroids in the treatment of children ranges from $7 to $12 per SFD gained. A social worker–based intervention had a cost-effectiveness ratio of $9 per SFD gained. What is it worth to patients, their families, and their health care providers to have an extra SFD?
Early Respiratory Infections, Asthma, and Allergy: 10-Year Follow-up of the Oslo Birth Cohort
Authors: Singh Anne Marie , Moss Mark H. 
Published: September 2006

Purpose of the Study.
As one dimension of the hygiene hypothesis, early infections may protect against the development of atopic disease. However, there are few long-term follow-up studies of the influence of early respiratory infections. This study investigates associations between early respiratory infections and diagnosed asthma, allergic rhinitis, and skin-prick sensitization in children at 10 years of age.

Study Population.
A total of 2540 Norwegian children were followed prospectively from birth to the age of 10 years in the Oslo Birth Cohort.

Methods.
Information on child’s health and environmental exposures, including experiences with respiratory infections, was recorded at birth and at 6 and 12 months. Current symptoms and “ever” doctor-diagnosed asthma and allergic rhinitis were compared with these early life exposures. A subset of the cohort underwent skin-prick testing.

Results.
“Ever” diagnosis of asthma was positively associated with measures of early life infection. Current asthma was related to lower respiratory tract infection (adjusted odds ratio [aOR]: 2.1; 95% confidence interval [CI]: 1.3–3.0) and croup (aOR: 2.3; 95% CI: 1.3–4.2) in the first year. ORs for allergic rhinitis and skin-prick sensitization were smaller but “mainly positive.” Birth order and child care attendance at 1 year of age were not significantly associated with any of the studied outcomes.

Conclusions.
Early respiratory infections did not protect against the development of atopic disease during the first 10 years of life. Rather, infections increased the risk for asthma at age 10.

Reviewer Comments.
The hygiene hypothesis has been used to explain an inverse relation between early-life infection and allergic disease. Although a number of studies have described the relationship of early childhood infections and atopic disease, few have done so prospectively. This study, with its ORs near 1 with narrow CIs, shows a positive relationship of infections to atopy. Thus, it does not support the view of protection with increasing infection, bringing to light that this relationship is not as simple or direct as was first described. Additional prospective studies with long-term follow-up are required to further define this relationship. In addition, these results support previous conclusions that early childhood infection may be associated with an increased risk for future development of asthma. There continues to be many unanswered questions regarding the risks in susceptible hosts.
A Prospective, Randomized, Double-blind, Placebo-Controlled Multi-centre Study on the Efficacy and Safety of Sublingual Immunotherapy (SLIT) in Children With Seasonal Allergic Rhinoconjunctivitis to Grass Pollen
Authors: Skripak Justin , Wood Robert A. 
Published: September 2006

Purpose of the Study.
Subcutaneous immunotherapy (SCIT) for seasonal allergic rhinitis is a well-established, effective, and potentially curative therapy. This study evaluated an alternate route for immunotherapy: the oral mucosa and gastrointestinal tract.

Study Population.
Ninety-seven children, aged 3 to 14 years, with seasonal allergic rhinitis and proven sensitivity to grass pollen were studied.

Methods.
Sensitivity to grass pollen was confirmed by positive skin-prick test, grass pollen–specific immunoglobulin E, and conjunctival provocation test. Patients were enrolled in a prospective, double-blind trial comparing sublingual immunotherapy (SLIT) to placebo. The treatment duration was 32 months. The primary outcome measure was the change in a multiple-symptom/medication score (which measured eye, nasal, and lung symptoms and rescue-medication use) after treatment. Data collected included patient-reported symptom scores and medication use, total and antigen-specific immunoglobulin E, skin-prick test, conjunctival provocation test, nasal provocation test, spirometry, exhaled nitric-oxide concentration, atopic dermatitis score, and eosinophilic cationic protein in nasal lavage fluid.

Results.
The multiple-symptom/medication score was significantly reduced by SLIT to 77.3% of the placebo group (P = .049). This overall score was affected mainly by a large reduction in rescue-medication usage among those in the treatment group (67% of placebo; P = .0025). There was no significant difference in any individual-symptom score.

Conclusion.
SLIT had a positive effect on rescue-medication usage but no significant effect on symptoms alone.

Reviewer Comments.
SLIT represents an alternative therapy with multiple potential advantages to SCIT, including the elimination of injections and improved safety profile. Several studies in adults and children have found improvement in symptom scores as well as reductions in medication use to the point where this is now being used in clinical practice in place of SCIT in many European countries. Additional studies, including investigation of optimal dosing and the potential to use multiple allergens, are needed to further define the future role of SLIT in the United States.
Passive Immunization During Pregnancy for Congenital Cytomegalovirus Infection
Authors: Maloney Jennifer M. , Sicherer Scott H. 
Published: September 2006

Purpose of the Study.
To investigate the effectiveness of cytomegalovirus (CMV)-specific hyperimmune globulin for primary CMV infection during pregnancy as a preventive therapy for fetal CMV infection.

Study Population.
One hundred fifty-seven pregnant women from 8 Italian cities with a primary CMV infection diagnosed via serologic testing.

Methods.
Women were placed in 1 of 2 groups. The therapy group comprised women who underwent amniocentesis and whose amniotic fluid contained either CMV detected by culture or CMV DNA detected by polymerase chain reaction. The group was offered intravenous CMV-specific hyperimmune globulin at a dose of 200 U per kg of maternal weight. Additional intravenous, intraumbilical-cord, or intra-amniotic doses were administered if evidence of persistent fetal involvement was present on ultrasound. Women with CMV-positive amniotic fluid who declined to receive hyperimmune-globulin infusions were followed as a comparison group. Those in the prevention group, consisting of women with a recent primary infection before 21 weeks’ gestation or who declined amniocentesis, were offered monthly hyperimmune globulin (100 U/kg intravenously). Pregnant women who declined monthly administration of hyperimmune globulin were followed as a comparison group.

Results.
In the therapy group, 31 women received hyperimmune globulin, only 1 (3%) of whom gave birth to an infant with symptomatic CMV disease, compared with 7 (50%) of 14 women who did not receive hyperimmune globulin. Thus, hyperimmune-globulin therapy was associated with a significantly lower risk of congenital CMV disease (adjusted odds ratio: 0.02; 95% confidence interval: −∞ to 0.15; P &lt; .001). In the prevention group, 37 women received hyperimmune globulin, 6 (16%) of whom had infants with congenital CMV infection, compared with 19 (40%) of 47 women who did not receive hyperimmune globulin. Thus, hyperimmune-globulin therapy was associated with a significantly lower risk of congenital CMV infection (adjusted odds ratio: 0.32; 95% confidence interval: 0.10 to 0.94; P = .04). No adverse effects resulted from CMV-specific hyperimmune globulin administration.

Conclusions.
Treatment of pregnant women with CMV-specific hyperimmune globulin is safe, and the findings of this nonrandomized study suggest that it may be effective in the treatment and prevention of congenital CMV infection. A controlled trial of this agent may be appropriate.

Reviewer Comments.
The risk of congenital CMV infection is high after primary maternal CMV infection. Although the majority of congenitally acquired CMV infections are asymptomatic, symptomatic infections result in significant morbidity and possible mortality. The implementation of CMV-specific hyperimmune globulin may reduce or prevent the devastating effects of symptomatic congenital CMV.
Exposure to Pets, and the Association With Hay Fever, Asthma, and Atopic Sensitization in Rural Children
Authors: Skripak Justin , Wood Robert A. 
Published: September 2006

Purpose of the Study.
To evaluate the effect of exposure to animals on the development of hay fever, asthma, and atopy.

Study Population.
Cross-sectional study of 2618 families of Swiss, German, and Austrian decent, living in a rural location. Families were assigned to 1 of 2 categories: farming and nonfarming.

Methods.
Information was collected by standardized questionnaire and interview. Mattress dust was collected and measured for content of endotoxin and cat allergen. Specific immunoglobulin E levels to multiple common allergens and immunoglobulin G4 to cat were measured.

Results.
Complete data were available for 812 children. Among them, 319 were farmers’ children and 493 were nonfarmers’ children. In the entire group, early (&lt;1-year-old) and current exposure to cats was associated with a reduced risk of wheezing and grass pollen sensitization. Current contact with dogs was inversely associated with hay fever, asthma, and sensitization to cat allergen and grass pollen. Early exposure to dog did not have any significant effects. When farm-animal contact was controlled for, most of these associations were weakened but were strongest in farmers’ children.

Conclusions.
There was an inverse relationship between dog exposure and asthma, hay fever, and allergy. However, much of this protective effect was explained by exposure to farm animals.

Reviewer Comments.
There are several studies that report pet exposure to be associated with a reduced risk for atopic disease. In this study, the primary outcome of decreased clinical manifestations of atopy was confounded by exposure to farm animals. Although the exposure to pets did not show an overall statistically significant association, the results approached significance, and a larger study population may have revealed significant differences. Also, the study ultimately found that animal exposure is most likely to provide a protective effect when the total level of exposure is highest (ie, those children exposed to pets and farm animals).
The Safety of Sublingual-Swallow Immunotherapy: An Analysis of Published Studies
Authors: Bollinger Mary Beth 
Published: September 2006

Purpose of the Study.
To perform a meta-analysis of all published controlled studies concerning sublingual-swallow immunotherapy (SLIT) to determine rates of adverse events (AEs).

Study Population.
Subjects were from 25 published studies (primarily European) aged 5 to 60 years (6 studies only enrolled children, 9 only adults, and the remainder a mix of both).

Methods.
A systematic Medline review from 1986 to May 2004 was performed. Twenty-five published double-blind, placebo-controlled studies using SLIT that included efficacy and safety data were analyzed. Twelve studies used a high allergen dose (defined as 50–500 times the standard subcutaneous dose), and 13 used a low allergen dose (defined as 1–50 times the subcutaneous dose). AEs were defined as local or systemic: local included oral itching and/or swelling and gastrointestinal complaints, and systemic reactions included skin reactions and ocular, nasal, and chest symptoms. The rates of AEs were compared between the groups. The allergens used in the studies included mites, grasses, trees, and ragweed (single-allergen treatments).

Results.
Combining the studies, there were a total of 445 subjects (405 placebo) in the high-allergen-dose group and 302 subjects (285 placebo) in the low-allergen-dose group. Children accounted for 103 total active-dose subjects. A total of 904 AEs were reported in the 198 553 active-allergen doses given, with 694 local reactions and 210 systemic reactions, with a rate of 0.15 to 0.2 reactions per patient. There were no reports of anaphylaxis. Overall, subjects in the low-allergen-dose group had significantly more local reactions than those in the high-dose group. However, there was no significant difference in the number of patients with AEs between the high- and low-allergen-dose groups when compared as a ratio of the number of SLIT doses received.

Conclusions.
This analysis found that local reactions were common with SLIT but were mild and self-resolved. Systemic reactions occurred rarely and were not dose dependent. The authors conclude that SLIT is safe for use in adults and children.

Reviewer Comments.
SLIT has been widely used in Europe in recent years, has been found to be efficacious by other studies, and has a good safety profile (supported by the meta-analysis). Another article in this same journal (Clin Exp Allergy. 2005;35:560–564) found SLIT to be safe in children younger than 5 years. SLIT is being studied in the United States as well and may be an option in the near future for treatment of allergic rhinitis.
Asthma-Related Health Care Resource Use Among Asthmatic Children With and Without Concomitant Allergic Rhinitis
Authors: Randolph Christopher 
Published: September 2006

Purpose of the Study.
To determine the incremental effect of allergic rhinitis on health care resource use in children with asthma.

Study Population.
Children (aged 6–15 years) with asthma and &gt;1 asthma-related encounter with a general practitioner (GP) during a 12-month follow-up period were included from the United Kingdom medical plus general-practice database, including 2 million office patient visits per year to &gt;500 GPs.

Methods.
This was a population-based historical cohort investigation. Asthma and allergic rhinitis were determined by diagnosis codes and drug codes for appropriate medications.

Results.
Of 9522 children with asthma, 1879 (19.7%) had allergic rhinitis recorded in the GP medical charts. Compared with children with asthma alone, children with comorbid allergic rhinitis experienced more GP visits (4.4 vs 3.4) and more of them were hospitalized for asthma (1.4% vs 0.5%) during the 12-month follow-up period. In multivariable regression analyses, comorbid allergic rhinitis was an independent predictor of hospitalization for asthma (odds ratio: 2.34; 95% confidence interval [CI]: 1.41–3.91) and was associated with increases in the number of asthma-related GP visits (mean increase: 0.53; 95% CI: 0.52–0.54) and asthma drug costs (mean increase [British pounds]: £6.7; 95% CI: £6.5–£7.0). The association between allergic rhinitis and higher costs of prescriptions for asthma drugs was independent of asthma severity, measured indirectly by the intensity of use of asthma drugs.

Conclusions.
Children with comorbid allergic rhinitis incurred greater prescription drug costs and experienced more physician visits and hospitalizations for asthma than did children with asthma alone. A unified treatment strategy for asthma and allergic rhinitis, as recommended by the Allergic Rhinitis and Its Impact on Asthma initiative, might reduce the costs of treating these conditions.

Reviewer Comments.
This is a useful study emphasizing the impact of allergic rhinitis on asthma, with implications for better therapeutic approaches. The study may have actually underestimated the impact of allergic rhinitis, because the data are retrospective and diagnosed allergic rhinitis was estimated at only 19.7%, compared with rates as high as 50% among children with asthma in other studies.
Early Childhood Environment Related to Microbial Exposure and the Occurrence of Atopic Disease at School Age
Authors: Skripak Justin , Wood Robert A. 
Published: September 2006

Purpose.
There has been much interest in the effect of various microbial exposures early in life on the subsequent development of atopic disease. This study aimed to examine the effects of several exposure types on atopic sensitization.

Study Population.
This was a cross-sectional study of 4111 Dutch schoolchildren aged 8 to 13 years.

Methods.
A questionnaire evaluating day care attendance before age 4, cats or dogs in the home before age 2, siblings, history of doctor-treated airway disease before age 2, and current respiratory status was used. Atopic status was tested by either skin-prick testing or antigen-specific immunoglobulin E levels to multiple common antigens.

Results.
Complete data were available for 1555 of the participants. Atopic sensitization was less frequent in children who attended day care (adjusted odds ratio: 0.74; 95% CI: 0.56–0.99) or had a pet in the home (adjusted odds ratio: 0.78; 95% CI: 0.61–0.99). There was no statistically significant association between the presence of siblings or the occurrence of doctor-treated airway disease and atopy.

Conclusion.
Day care attendance and having a pet in the home may provide a protective effect against atopic sensitization.

Reviewer Comments.
This study attempts to help clarify factors that may be associated with the primary development of atopy, which has been an area of great interest, especially given the rising prevalence of allergic disease. The results are consistent with many other studies indicating that microbial exposure early in life may have a preventive effect. Additional studies, including prospective cohorts, are being performed to define these associations more clearly. With luck, one day we will be able to use this information to design effective preventive strategies.