Karen Riedlinger

Incidence of herpes zoster, 1997-2002.

We estimated age-specific herpes zoster (HZ) incidence rates in the Kaiser Permanente Northwest Health Plan (KPNW) during 1997-2002 and tested for secular trends and differences between residents of two states with different varicella vaccine coverage rates. The cumulative proportions of 2-year-olds vaccinated increased from 35% in 1997 to 85% in 2002 in Oregon, and from 25% in 1997 to 82% in 2002 in Washington. Age-specific HZ incidence rates in KPNW during 1997-2002 were compared with published rates in the Harvard Community Health Plan (HCHP) during 1990-1992. The overall HZ incidence rate in KPNW during 1997-2002 (369/100,000 person-years) was slightly higher than HCHPs 1990-1992 rate when adjusted for age differences. For children 6-14 years old, KPNWs rates (182 for females, 123 for males) were more than three times HCHPs rates (54 for females, 39 for males). This increase appears to be associated with increased exposure of children to oral corticosteroids. The percentage of KPNW children exposed to oral corticosteroids increased from 2.2% in 1991 to 3.6% in 2002. Oregon residents had slightly higher steroid exposure rates during 1997-2002 than Washington residents. There were significant increases in HZ incidence rates in Oregon and Washington during 1997-2002 among children aged 10-17 years, associated with increased exposure to oral steroids.

Identifying pregnancy episodes, outcomes, and mother-infant pairs in the Vaccine Safety Datalink

BACKGROUND The need for research on the safety of vaccination during pregnancy is widely recognized. Large, population-based data systems like the Vaccine Safety Datalink (VSD) may be useful for this research, but identifying pregnancies using electronic medical record (EMR) and claims data can be challenging. METHODS We modified an existing data processing algorithm to identify pregnancies within seven of the ten VSD sites. We validated the algorithm by calculating the agreement in pregnancy outcome type, end date, and gestational age between the algorithm and manual medical record review. At each participating site, we randomly sampled 15 episodes within four outcome type strata (live births, spontaneous abortions, elective abortions, and other pregnancy outcomes) for a total of 60 episodes per site. We also developed and validated methods to link mothers to their infants in the electronic data. RESULTS We identified 595,929 pregnancy episodes ending in 2002 through 2006 among women 12 through 55 years of age. Of these pregnancies, 75% ended in live births, 12% in spontaneous abortions, and 9% in elective abortions. We were able to confirm a pregnancy within 28 days of the algorithm-estimated pregnancy start date for 99% of live births, 93% of spontaneous abortions, 92% of elective abortions, and 90% of other outcomes sampled. The agreement between the algorithm-identified and the abstractor-identified outcome date ranged from 70% (elective abortion) to 96% (live birth) depending on outcome type. When gestational age was available in the EMR, agreement ranged from 82% (other) to 98% (live birth) depending on outcome type. We confirmed 100% of the 350 sampled mother-infant linkages with manual medical record review. CONCLUSIONS The VSD algorithm accurately identifies pregnancy episodes and mother-infant pairs across participating sites. Additional manual record review may be needed to improve the precision of the pregnancy date estimates depending on specific study needs. These algorithms will allow us to conduct large, population-based studies of the safety of vaccination during pregnancy.

Laboratory Diagnosis and Characteristics of Breakthrough Varicella in Children

The atypical features of varicella in vaccinated persons (breakthrough varicella [BTV]) present diagnostic challenges. We examined varicella-zoster virus (VZV) polymerase chain reaction (PCR) and immunoglobulin (Ig) M and IgG serologic test results for confirming BTV cases. Among 33 vaccinated children with varicella-like rash, we identified wild-type VZV in 58% overall and in 76% of those with adequate tissue specimens; no vaccine-type virus was found. Of the 12 subjects with PCR-confirmed BTV and acute-phase serum samples, 9 had detectable IgM, and all had highly elevated acute-phase IgG titers. Six subjects with negative PCR results had lower IgG titers and negative IgM results. Although PCR is the preferred method for laboratory confirmation of BTV, a positive serum varicella IgM test result should also be considered to be diagnostic in a suspected BTV case; however, a negative IgM test result cannot be used to rule out the diagnosis. The value of highly elevated IgG titers needs further evaluation. Larger studies are needed to confirm these results.

Completion and timing of the three-dose human papillomavirus vaccine series among adolescents attending school-based health centers in Oregon

OBJECTIVE Many adolescents do not complete the 3-dose human papillomavirus vaccine series in the recommended time frame, or at all. Given the challenges of administering a multi-dose vaccine to adolescents, especially those in vulnerable populations, we evaluated completion of the human papillomavirus vaccine series in 19 of Oregons school-based health centers. METHODS Among persons aged 0-17 who initiated the human papillomavirus vaccine series at a study school-based health center in 2007, we identified all subsequent human papillomavirus doses administered at the school-based health centers, or found in Oregons immunization information system, in 2007-2008. We describe the proportion completing the vaccine series and mean intervals between doses, stratified by age, race, and insurance status. RESULTS Four hundred fifty persons initiated the human papillomavirus series in 2007. By December 2008, 51% of these had received all 3 doses. Series completion increased significantly with age, differed significantly between race groups (highest among white persons (56%); lowest among black persons (38%)), and did not differ significantly by insurance status. Mean intervals between doses did not differ significantly by race or insurance status. CONCLUSIONS Even in challenging conditions, school-based health centers provide excellent preventive care to vulnerable youth. These results support the importance of maintaining and expanding school-based health center access in vulnerable adolescent populations.

Reported adverse events in young women following quadrivalent human papillomavirus vaccination.

PURPOSE To assess and describe young womens experiences with their first dose of quadrivalent human papillomavirus vaccine (HPV4) (Gardasil®) in a large managed care organization. METHODS We collected survey and electronic medical record (EMR) data for 899 young women aged 11-26 receiving their first HPV4 injection from February through September 2008. Survey items included questions about adverse events, interactions with healthcare providers, and knowledge and attitudes toward HPV disease and HPV4. RESULTS Six hundred ninety-six (78%) participants reported pain at the injection site. Other common reactions included injection site bruising or discoloration (n=155, 17%) or swelling (n=127, 14%) and presyncope or syncope (n=134, 15%). Overall, preteens and teens were more likely than adult participants to report vaccine adverse events. Most respondents, particularly in the adult age group, reported that their healthcare provider reviewed important information about HPV infection and about the risks and benefits of receiving the vaccine. Knowledge and attitudes about HPV and HPV4 also varied by age, with older women generally exhibiting more accurate knowledge about HPV and perceived susceptibility to cervical cancer. CONCLUSIONS There were significant age differences in young womens experiences with their first HPV4 injection. These findings highlight the importance of age-appropriate education and provider communications about HPV disease and vaccination.

Laboratory characteristics of suspected herpes zoster in vaccinated children.

Varicella vaccination of children has decreased varicella disease incidence, but introduced the occurrence of herpes zoster (HZ) from vaccine-type virus. We identified 14 vaccinated children with suspected HZ and confirmed varicella virus by polymerase chain reaction in 6 cases. Two cases were due to vaccine-type virus. Serum varicella IgM and IgG were not useful for diagnosis of HZ among vaccinated children.

Passive Cigarette Smoke Exposure and Other Risk Factors for Invasive Pneumococcal Disease in Children: A Case-Control Study

OBJECTIVE To investigate whether passive cigarette smoke exposure increases the risk of invasive pneumococcal disease in children. METHODS In a population-based case-control study, 171 children aged 0 to 12 years with culture-confirmed invasive pneumococcal disease during the years 1994 to 2004 were identified. Two controls were matched to each case on age and patterns of Health Plan membership. We reviewed medical records of subjects and family members for information on household cigarette smoke exposure within 2 years of the diagnosis of invasive pneumococcal disease. We collected information on sex, race, pneumococcal vaccination, selected medical conditions, and medications in the 3 months before the diagnosis. RESULTS Similar proportions of cases (25%) and controls (30%) had definite or probable passive smoke exposure (odds ratio [OR] = 0.76, 95% confidence interval [CI] = 0.47-1.2). Cases of invasive pneumococcal disease were more likely to be nonwhite than controls (OR = 4.4, 95% CI = 2.3-8.2). Elevated risk of invasive pneumococcal disease was found in subjects with recent pulmonary diagnoses (OR = 2.2, 95% CI = 1.2-4.0) and recent antibiotic use (OR = 1.6, 95% CI = 1.1-2.3). CONCLUSIONS Passive cigarette smoke exposure was not associated with invasive pneumococcal disease in this pediatric population. Invasive pneumococcal disease was associated with recent pulmonary diagnoses and recent antibiotic use.

PS3-6: Blood Safety Continuous Active-Surveillance Network Feasibility Evaluation (Blood-SCAN)

Background/Aims In 2011, the US Food and Drug Administration (FDA) created the Blood Safety Continuous Active-Surveillance Network (Blood-SCAN), the first nationwide active surveillance system for monitoring the safety of FDA-regulated blood components and blood-derived products. Blood-SCAN employs the Mini-Sentinel Distributed Database (MSDD) which contains 126 million individuals within 17 Data Partners. Blood-SCAN is intended to augment the existing safety surveillance system and improve US biovigilance efforts. As a first step in creating Blood-SCAN, we assessed the feasibility of using the current MSDD to evaluate blood component and blood-derived product exposures and related health outcomes. Methods The assessment consisted of 4 activities: (1) an expert working group identified 20 blood components and blood-derived products and 10 health outcomes of interest (HOIs) to evaluate the data available in the MSDD, (2) a literature scan was conducted to identify electronic algorithms to capture these product exposures and HOIs, (3) HOI and exposure frequencies were tabulated using established Mini-Sentinel programs, and (4) structured discussions were conducted with all Mini-Sentinel Data Partners to assess the availability, content, and quality of data within their databases. Results Claims codes were available for all of the blood components and blood-derived products, and many of the claims codes for blood-derived products were sufficiently specific to allow analyses by product manufacturer, fulfilling an important regulatory need. Adequate counts of exposures to immunoglobulin products indicate the potential for future surveillance studies on these products. MSDD analyses suggest that blood-derived products are captured effectively in outpatient settings but not in inpatient settings, limiting the scope of therapeutic indications that can be assessed. Blood component exposures are also captured in outpatient settings within the MSDD; however, because most transfusions occur in inpatient settings, these data may not be completely representative of the patient population, reason for transfusion, and dose. Most Data Partners reported no current ability to access inpatient blood component exposures through existing claims data streams. Conclusions The current MSDD supports safety surveillance for a variety of blood components and blood-derived products in the outpatient setting. Expanding the MSDD to include inpatient data streams will ensure that Blood-SCAN achieves its full potential.

PS1-33: CESR Proof-of-Concept Projects: Lessons Learned from the DCC Perspective

Background/Aims Two multi-site proof-of-concept projects were initiated to demonstrate the viability and sustainability of the newly created Kaiser Permanente (KP) Center for Effectiveness and Safety Research (CESR). This presentation highlights lessons learned from the Data Coordinating Center (DCC) perspective as both projects conclude. Methods Each proof-of-concept project, charged with finishing within one year of start-up, assembled teams, including investigators and programmers from each KP site. CESR’s DCC supplied an overall project manager as well as consultation services on Institutional Review Board (IRB) issues, Data Use and Sharing Agreements(DUSA) and secure transfer of collected data. Other DCC services included SAS multi-site extraction programs for Virtual Data Warehouse (VDW) data and other non-VDW data. When non-VDW data was requested, the DCC also defined specifications for these tables. Cleaning of, Quality Assurance (QA) of and final combination of data from multiple sites was performed at the DCC. Results The proof-of-concept projects helped to refine CESR processes for future projects. Lessons learned include 1) consult a VDW specialist early in the planning process, including before IRB submission; 2) describe data to be extracted and outlined in IRB applications and DUSAs broadly enough to include related variables to minimize the number of time-consuming modifications (e.g., ask for newborn statistics, not head circumference or agpar5); 3) create and use templates for extraction programs, for programs which combine multi-site data and simple statistical processes; 4) date stamp programs and returning datasets and related output; 5) develop one location to allow investigators and programmers to access project related information and documents; 6) develop documents for tracking programs (including modifications) and datasets flowing between multiple sites and data coordinating center; and 7) invest time to create, update and communicate data flow diagrams (DFD) for each SAS program sent to sites. Conclusions Documenting and analyzing the processes involved in proof-of-concept projects can help inform and contribute to efficiencies in future projects.

PS1-17: Herpes Zoster in Children

Background and Aims: Vaccine-strain herpes zoster (HZ) is a potential adverse outcome of varicella vaccination. Data are needed on the incidence of and risk factors for vaccine-strain HZ among children <18 years of age. The Centers for Disease Control and Prevention (CDC) funded a study at Kaiser Permanente Northwest (KPNW) to determine the number and proportion of pediatric HZ cases caused by varicella vaccine, assess positive predictive value (PPV) of physician diagnosis of HZ, and compute incidence of vaccine and wild-type HZ in the KPNW population. Methods: We used electronic data to identify all pediatric medical office visits with a HZ diagnosis. During the visit, the provider collected a lesion specimen and completed a questionnaire. The study nurse called to interview the parent and, if no specimen was previously collected, schedule a home visit to obtain it. A follow-up questionnaire on severity and duration of HZ was returned four weeks after rash onset. Specimens were sent to the National Varicella-Zoster Virus (VZV) Laboratory at the CDC for PCR analysis to confirm presence of the virus and classify it as wild-type or vaccine-type. Results: From 5/2005 to 3/2009, we enrolled 308 subjects in the study. Two-hundred eighty-one (96%) had adequate lesion specimens for PCR analysis. We found VZV in 75% of adequate specimens; 69% were wild-type, while 9% were vaccine-type and 1% (2) were vaccine:wild-type recombination. Among vaccinated subjects, 69% had wild-type HZ. The PPV for provider diagnosis of ‘definite HZ’ was 83%: 85% for unvaccinated subjects and 76% for vaccinated subjects. Incidence rates for vaccine-strain and wild-type VZV in plan children age 0–17 will be presented. Conclusions: Vaccine-strain VZV was found in a minority of HZ cases in this age group. We observed recombination of vaccine-strain and wild-type viruses in two subjects. Provider diagnosis of HZ was good overall.