Vaccine Delays, Refusals, and Patient Dismissals: A Survey of Pediatricians.

BACKGROUND: Parental noncompliance with the American Academy of Pediatrics and Centers for Disease Control and Prevention immunization schedule is an increasing public health concern. We examined the frequency of requests for vaccine delays and refusals and the impact on US pediatricians' behavior. METHODS: Using national American Academy of Pediatrics Periodic Surveys from 2006 and 2013, we describe pediatrician perceptions of prevalence of (1) vaccine refusals and delays, (2) parental reasons for refusals and/or delays, and (3) physician dismissals. Questions about vaccine delays were asked only in 2013. We examined the frequency, reasons for, and management of both vaccine refusals and delays by using bivariate and multivariable analyses, which were controlled for practice characteristics, demographics, and survey year. RESULTS: The proportion of pediatricians reporting parental vaccine refusals increased from 74.5% in 2006 to 87.0% in 2013 (P < .001). Pediatricians perceive that parents are increasingly refusing vaccinations because parents believe they are unnecessary (63.4% in 2006 vs 73.1% in 2013; P = .002). A total of 75.0% of pediatricians reported that parents delay vaccines because of concern about discomfort, and 72.5% indicated that they delay because of concern for immune system burden. In 2006, 6.1% of pediatricians reported "always" dismissing patients for continued vaccine refusal, and by 2013 that percentage increased to 11.7% (P = .004). CONCLUSIONS: Pediatricians reported increased vaccine refusal between 2006 and 2013. They perceive that vaccine-refusing parents increasingly believe that immunizations are unnecessary. Pediatricians continue to provide vaccine education but are also dismissing patients at higher rates.

The disease burden of pertussis in adults 50 years old and older in the United States: a retrospective study.

BACKGROUND: While the incidence of pertussis has increased in adolescents and adults in recent years in the U.S., little is known about the incidence and economic burden of pertussis in older adults. This study provides evidence of the incidence of pertussis and direct medical charges associated with pertussis episodes of care (PEOCs) in adults aged 50 years and older in the U.S. METHODS: PEOCs were divided into periods before and after the initial pertussis diagnosis was made (i.e., the index date) to capture any conditions immediately preceding the pertussis diagnosis that may have represented misdiagnoses and subsequent conditions that may have represented sequelae. Data were extracted from IMS's recently acquired SDI databases of longitudinal, patient-level practitioner claims and hospital operational billing records collected from private practitioners and hospitals, respectively, across the U.S. Patients 50 years and older with one or more ICD-9-CM diagnoses for pertussis/whooping cough and/or a laboratory test positive for Bordetella pertussis between 1/1/2006 and 10/31/2010 were eligible for study inclusion. Resource utilization and charges (i.e., unadjudicated claims) associated with the patient's physician and hospital care were analyzed. The nationally projected incidence of pertussis was estimated using a subsample of patients with the required data necessary for projection. RESULTS: Estimated incidence of diagnosed pertussis ranged from 2.1-4.6 cases per 100,000 people across the two age groups (50-64 and [greater than or equal to] 65) during the years 2006 to 2010. The analysis of charges included 5,748 patients [greater than or equal to] 50 years of age with pertussis. Average charges across the entire episode of care were $1,835 and $14,428 per patient in the outpatient and inpatient settings, respectively. The average number of outpatient (i.e., private practitioner) visits was 2 per patient in both the pre-index and post-index periods. CONCLUSIONS: In the U.S., the incidence of diagnosed pertussis in adults 50 years and older has increased between 2006 and 2010. Healthcare utilization and charges associated with pertussis are substantial, suggesting the need for additional prevention and control strategies and a higher degree of clinical awareness on the part of health care providers. Additional research regarding pertussis in older populations is needed to substantiate these findings.

Caregiver preferences for pediatric asthma treatment delivery systems.

This study was conducted to assess caregiver preferences for pediatric asthma treatment delivery systems. A total of 186 caregivers of children with asthma who ranged in age from 1 to 4 y completed a stated-preference questionnaire to assess the importance of specific treatment attributes in terms of caregivers' preferences, and to determine the percentages of caregivers who preferred specific treatments. Other outcomes assessed included caregivers' likelihood of adhering to pediatric asthma treatment. Most respondents (75%) preferred treatments that have been approved by the US Food and Drug Administration (FDA) in children as young as 12 mo, that require minimal effort in coordination and inhalation on the child's part, and that take up to 10 min to administer. A greater proportion of respondents indicated that they would be able to follow the physician's advice (increased likelihood of adherence) if given this treatment (54%) versus an alternative (35%). This difference did not achieve statistical significance, however. The conjoint analysis method used in this study enabled investigators to assess caregivers' relative preferences for specific attributes of various pediatric asthma treatments. Overall, FDA approval in children as young as 12 mo was the most preferred attribute. Caregiver preference for pediatric asthma treatment alternatives is an important consideration and should be a component of discussions between healthcare professionals and caregivers.

Rationale for use of Tdap booster vaccines for adolescent immunization: overview of efficacy, safety, and clinical use.

Pertussis is one of the only vaccine-preventable diseases with increasing incidence in the United States. The incidence of pertussis infection in adolescents is a growing concern; it can be a severe disease that may lead to significant morbidity and mortality when transmitted to susceptible populations (eg, infants). Experts have conceded that booster vaccination of adolescents may considerably decrease the incidence of pertussis infections in previously immunized, partially immunized, and nonimmunized populations. Studies in 2 tetanus, diphtheria, and acellular pertussis (Tdap) booster vaccines licensed by the Food and Drug Administration (FDA) have shown efficacy against pertussis disease and have demonstrated a safety profile comparable to tetanus and diphtheria vaccine (Td) in adolescents. Immunization schedules now include use of Tdap vaccines for preadolescent and adolescent populations to counter the increase in pertussis outbreaks. Challenges for clinicians include prompt recognition of pertussis symptoms, proper diagnosis using appropriate tools, and timely reporting of pertussis infections to surveillance bodies. Additional studies are needed to monitor trends of pertussis incidence after implementing the new vaccination schedule for adolescents.

Functional studies on the ligand-binding domain of Ultraspiracle from Drosophila melanogaster.

The functional insect ecdysteroid receptor is comprised of the ecdysone receptor (EcR) and Ultraspiracle (USP). The ligand-binding domain (LBD) of USP was fused to the GAL4 DNA-binding domain (GAL4-DBD) and characterized by analyzing the effect of site-directed mutations in the LBD. Normal and mutant proteins were tested for ligand and DNA binding, dimerization, and their ability to induce gene expression. The presence of helix 12 proved to be essential for DNA binding and was necessary to confer efficient ecdysteroid binding to the heterodimer with the EcR (LBD), but did not influence dimerization. The antagonistic position of helix 12 is indispensible for interaction between the fusion protein and DNA, whereas hormone binding to the EcR (LBD) was only partially reduced if fixation of helix 12 was disturbed. The mutation of amino acids, which presumably bind to a fatty acid evoked a profound negative influence on transactivation ability, although enhanced transactivation potency and ligand binding to the ecdysteroid receptor was impaired to varying degrees by mutation of these residues. Mutations of one fatty acid-binding residue within the ligand-binding pocket, 1323, however, evoked enhanced transactivation. The results confirmed that the LBD of Ultraspiracle modifies ecdysteroid receptor function through intermolecular interactions and demonstrated that the ligand-binding pocket of USP modifies the DNA-binding and transactivation abilities of the fusion protein.