S. Elizabeth Williams

A Randomized Trial to Increase Acceptance of Childhood Vaccines by Vaccine-Hesitant Parents: A Pilot Study

OBJECTIVE A cluster randomized trial was performed to evaluate an educational intervention to improve parental attitudes and vaccine uptake in vaccine-hesitant parents. METHODS Two primary care sites were randomized to provide families with either usual care or an intervention (video and written information) for vaccine-hesitant parents. Eligible parents included those presenting for their childs 2-week well-child visit with performance on the Parent Attitudes about Childhood Vaccines (PACV) survey suggesting vaccine hesitancy (score ≥25). Enrollees completed PACV surveys at the 2-month well-child visit and vaccination status at 12 weeks of age was assessed. The primary outcome was the difference in PACV scores obtained at enrollment and 2 months between the 2 groups. The proportion of on-time vaccination was also compared at 12 weeks. RESULTS A total of 454 parents were approached, and 369 (81.3%) participated; 132 had PACV scores of ≥25 and were enrolled, 67 in the control group (mean PACV score 37) and 55 in the intervention group (mean PACV score 40). Two-month PACV surveys were completed by 108 (∼90%) of enrollees. Parents in the intervention group had a significant decrease in PACV score at 2 months compared to control (median difference 6.7, P = .049); this remained significant after adjustment for baseline PACV score, race/ethnicity, and income (P = .044). There was no difference in the on-time receipt of vaccines between groups at 12 weeks. CONCLUSIONS A brief educational intervention for vaccine-hesitant parents was associated with a modest but significant increase in measured parental attitudes toward vaccines.

Overview of the Clinical Consult Case Review of adverse events following immunization: Clinical Immunization Safety Assessment (CISA) network 2004–2009

BACKGROUND In 2004 the Clinical Consult Case Review (CCCR) working group was formed within the CDC-funded Clinical Immunization Safety Assessment (CISA) Network to review individual cases of adverse events following immunizations (AEFI). METHODS Cases were referred by practitioners, health departments, or CDC employees. Vaccine Adverse Event Reporting System (VAERS) searches and literature reviews for similar cases were performed prior to review. After CCCR discussion, AEFI were assessed for a causal relationship with vaccination and recommendations regarding future immunizations were relayed back to the referring physicians. In 2010, surveys were sent to referring physicians to determine the utility and effectiveness of the CCCR service. RESULTS CISA investigators reviewed 76 cases during 68 conference calls between April 2004 and December 2009. Almost half of the cases (35/76) were neurological in nature. Similar AEFI for the specific vaccines received were discovered for 63 cases through VAERS searches and for 38 cases through PubMed searches. Causality assessment using the modified WHO criteria resulted in classifying 3 cases as definitely related to vaccine administration, 12 as probably related, 16 as possibly related, 18 as unlikely related, 10 as unrelated, and 17 had insufficient information to assign causality. The physician satisfaction survey was returned by 30 (57.7%) of those surveyed and a majority of respondents (93.3%) felt that the CCCR service was useful. CONCLUSIONS The CCCR provides advice about AEFI to practitioners, assigns potential causality, and contributes to an improved understanding of adverse health events following immunizations.

Live vaccine use and safety in DiGeorge syndrome.

OBJECTIVE: Live vaccines are generally contraindicated in patients with DiGeorge syndrome (DGS), a congenital disorder characterized by cellular immune deficiency. Vaccine utilization and safety in this population are not well described. This study examined vaccination patterns and adverse events following live immunization (AEFLI) in these individuals. METHODS: A multicenter retrospective cohort study was conducted in subjects with DGS confirmed by fluorescence in situ hybridization assay (chromosome 22q11.2 microdeletion). Live vaccine-preventable illnesses, vaccination coverage and timeliness, and AEFLIs in the 56-day window after live vaccination were examined. Bivariate and multivariable analyses assessed the impact of demographics medical history, timing of diagnostic confirmation, and preceding immune function on vaccination patterns and AEFLIs. RESULTS: Of 194 subjects, 77% and 75% received measles-mumps-rubella (MMR) and varicella vaccines, respectively; 58% completed recommended vaccinations by age 19 to 35 months. Adverse events occurred after 14% and 20% of MMR and varicella vaccine doses, respectively. Most events were minor, few were serious, and no deaths were reported in post–live vaccination windows. Although early diagnostic confirmation negatively affected live vaccination coverage and timeliness (P < .001), baseline CD4% did not differ between subjects who did or did not receive live vaccines by 12 to 18 months. Among varicella vaccine recipients, those with a subsequent adverse event had a lower preceding CD4% (24.8% ± 7.3%) than those without (35.5% ± 11.7%) (P < .05); no CD4% differences were observed with MMR vaccination. Fourteen unvaccinated subjects experienced live vaccine–preventable illnesses. CONCLUSIONS: Live vaccines were frequently given and generally well-tolerated among patients with DGS with mild-to-moderate immunosuppression.

Formal training in vaccine safety to address parental concerns not routinely conducted in U.S. pediatric residency programs

OBJECTIVE To determine if U.S. pediatric residency programs provide formal training in vaccine safety to address parental vaccine concerns. METHODS An electronic survey was mailed to all members of the Association of Pediatric Program Directors (APPD) to assess (1) if U.S. pediatric residency programs were providing formal vaccine safety training, (2) the content and format of the training if provided, and (3) interest in a training module for programs without training. Two follow-up surveys were mailed at 2 week intervals. Responses to the survey were collected at 4 weeks following the last mailing and analyzed. Logistic regression was used to assess the impact of program size on the likelihood of vaccine safety training. Pearsons chi square was used to compare programs with and without formal vaccine safety training in 5 U.S. regions. RESULTS The survey was sent to 199 APPD members; 92 completed the survey (response rate 46.2%). Thirty-eight respondents (41%) had formal training in vaccine safety for pediatric residents at their programs; 54 (59%) did not. Of those that did not, the majority (81.5%) were interested in formal vaccine safety training for their residents. Of all respondents, 78% agreed that training in vaccine safety was a high priority for resident education. Thirty-five percent of all respondents agreed that local parental attitudes about vaccines influenced the likelihood of formal vaccine safety training. CONCLUSION Most pediatric residency programs surveyed do not include formal training on vaccine safety; yet, such training is supported by pediatric residency program directors as a priority for pediatric residents.

A systematic review of validated methods for identifying uveitis using administrative or claims data

PURPOSE To review algorithms used to identify uveitis in administrative and claims databases. METHODS We searched the MEDLINE database via PubMed from 1991 to September 2012 using vocabulary and key terms related to uveitis. We also searched the reference lists of included studies. Two investigators independently assessed studies against pre-determined inclusion criteria. The same two investigators independently extracted data regarding participant and algorithm characteristics and assessed a studys methodological rigor using a pre-defined approach. RESULTS Seven studies met inclusion criteria. Variability exists among algorithms employed in these studies for finding cases of uveitis and related conditions as well as in use and implementation of validation methods. Of the seven included studies, three involved case validation. One used a narrow algorithm in addition to text mining of electronic medical records to identify incident cases and found a positive predictive value of 52.1%. The other two, which used broader uveitis definitions and included both incident and prevalent cases, found positive predictive values of 24.8% and 52.6%. CONCLUSIONS Further research, with case as well as individual code validation, is needed to determine appropriate uveitis algorithms for purposes of active surveillance in administrative data. Decisions about which algorithm to use will depend on the desired balance of sensitivity and specificity.

A systematic review of validated methods to capture several rare conditions using administrative or claims data

PURPOSE To identify and assess billing, procedural, or diagnosis code, or pharmacy claim-based algorithms used to identify the following health outcomes in administrative and claims databases: acute disseminated encephalomyelitis (ADEM), optic neuritis, tics, and Henoch Schönlein purpura (HSP). METHODS We searched the MEDLINE database from 1991 to September 2012 using controlled vocabulary and key terms related to the conditions. We also searched the reference lists of included studies. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria and extracted case validation data from those studies meeting inclusion criteria. RESULTS Two eligible studies addressed ADEM, two addressed optic neuritis, and four studies addressed tics. Only one study addressed HSP. Among these, one study of ADEM reported a positive predictive value of 66%, however the identification algorithm contained a combination of International Classification of Diseases (ICD) codes and other identification methods and the performance of the ICD-9 codes alone was not reported. No other studies reported validation data. CONCLUSIONS The lack of data on the validity of algorithms to identify these conditions may hamper our ability to determine incidence patterns with respect to infection and vaccination exposures. Further epidemiologic research to define validated methods of identifying cases could improve surveillance using large linked healthcare databases.

A systematic review of validated methods for identifying transverse myelitis using administrative or claims data

PURPOSE To identify and assess billing, procedural, or diagnostic code algorithms used to identify transverse myelitis in administrative databases. METHODS We searched the MEDLINE database from 1991 to September 2012 using controlled vocabulary and key terms related to transverse myelitis. We also searched the reference lists of included studies. Two investigators independently assessed the full text of studies against pre-determined inclusion criteria. Two reviewers independently extracted data regarding participant and algorithm characteristics. RESULTS Three studies met criteria for inclusion in this review. The only algorithm based solely on administrative claims data with a reported positive predictive value included five ICD-9 codes (codes 341.20, 341.21, 341.22, 323.8, 323.9). The positive predictive value for physician-diagnosed acute transverse myelitis was 62%. CONCLUSIONS More research is needed to establish an accurate algorithm to identify transverse myelitis in large administrative databases using diagnosis and/or procedure codes. Use of standardized consensus definitions, clear description for algorithm selection, and reporting of validation procedure and results would be most beneficial.

Clinical assessment of serious adverse events in children receiving 2009 H1N1 vaccination.

Background: Monovalent 2009 H1N1 influenza vaccines were licensed and administered in the United States during the H1N1 influenza pandemic between 2009 and 2013. Methods: Vaccine Adverse Event Reporting System received reports of adverse events following immunization (AEFI) after H1N1 vaccination. Selected reports were referred to the Centers for Disease Control and Prevention’s Clinical Immunization Safety Assessment network for additional review. We assessed causality using modified World Health Organization criteria. Results: There were 3,928 reports of AEFI in children younger than age 18 years after 2009 H1N1 vaccination received by January 31, 2010. Of these, 214 (5.4%) were classified as serious nonfatal and 109 were referred to Clinical Immunization Safety Assessment for further evaluation. Ninety-nine (91%) had sufficient initial information to begin investigation and are described here. The mean age was 8 years (range, 6 months–17 years) and 38% were female. Median number of days between vaccination and symptom onset was 2 (range, −11 days to +41 days). Receipt of inactivated, live attenuated, or unknown type of 2009 H1N1 vaccines was reported by 68, 26 and 5 cases, respectively. Serious AEFI were categorized as neurologic events in 47 cases, as hypersensitivity in 15 cases and as respiratory events in 10 cases. At the time of evaluation, recovery was described as complete (61), partial (16), no improvement (1), or unknown (21). Causality assessment yielded the following likelihood of association with 2009 H1N1 vaccination: 8 definitely; 8 probably; 21 possibly; 43 unlikely; 17 unrelated; and 2 unclassifiable. Conclusions: Most AEFI in children evaluated were not causally related to vaccine and resolved without sequelae. Detailed clinical assessment of individual serious AEFI can provide reassurance of vaccine safety.