James D. Nordin

Influenza Vaccine Effectiveness in Preventing Hospitalizations and Deaths in Persons 65 Years or Older in Minnesota, New York, and Oregon: Data from 3 Health Plans

This study developed methods and determined the impact of influenza vaccination on elderly persons in 3 large health plans: Kaiser Permanente Northwest, HealthPartners, and Oxford Health Plans. Data for the 1996-1997 and 1997-1998 seasons were extracted from administrative databases. Subjects were health plan members > or = 65 years old. Comorbid conditions collected from the preceding year were used for risk adjustment with logistic regression. The virus-vaccine match was excellent for year 1 and fair for year 2. Both years, during peak and total periods, vaccination reduced all causes of death and hospitalization for pneumonia and influenza: hospitalizations were reduced by 19%-20% and 18%-24% for years 1 and 2, respectively, and deaths were reduced by 60%-61% and 35%-39% for the same periods. These results show that all elderly persons should be immunized annually for influenza. The methods used in this study are an efficient cost-effective way to study vaccine impact and similar questions.

Population-Based Incidence of Pertussis among Adolescents and Adults, Minnesota, 1995–1996

To estimate the incidence of pertussis, a prospective study was done among members of a managed care organization in Minneapolis/St. Paul, Minnesota. Of 212 patients 10-49 years old enrolled from January 1995 through December 1996, 8 were found to be culture positive, 10 were found to be positive by polymerase chain reaction assay, 13 had a > or =2-fold increase in IgG or IgA to pertussis toxin (PT), and 18 had IgG to PT in a single serum specimen > or =3 SD above the mean of an age-matched control group. At least 1 positive laboratory test result for pertussis infection was found in 27 (13%) patients, among whom the duration of cough illness was a median of 42 days (range, 27-66 days). On the basis of any positive laboratory result, the estimated annual incidence of pertussis was 507 cases per 100,000 person-years (95% confidence interval, 307-706 cases). Bordetella pertussis infection may be a more common cause of cough illness among adolescents and adults than was recognized previously.

Influence of High-Risk Medical Conditions on the Effectiveness of Influenza Vaccination among Elderly Members of 3 Large Managed-Care Organizations

This serial cohort study assessed the risk of hospitalization or death associated with influenza and the effectiveness of influenza vaccination among subgroups of elderly members of 3 managed-care organizations in the United States. Data on baseline characteristics and outcomes were obtained from computerized databases. A total of 122,974 (1996-1997 season) and 158,454 (1997-1998 season) persons were included in the cohorts. Among unvaccinated persons, hospitalizations for pneumonia/influenza or death occurred in 8.2 of 1000 healthy and 38.4 of 1000 high-risk persons in year 1, and in 8.2 of 1000 healthy and 29.3 of 1000 high-risk persons in year 2. After adjustments, vaccination was associated with a 48% reduction in the incidence of hospitalization or death (95% confidence interval [CI], 42-52) in year 1 and 31% (95% CI, 26-37) in year 2. Effectiveness estimates were statistically significant and generally consistent across the healthy and high-risk subgroups. The absolute risk reduction, however, was 2.4- to 4.7-fold higher among high-risk than among healthy elderly persons. All elderly individuals may substantially benefit from vaccination. However, the impact of influenza is greater in persons with high-risk medical conditions.

Active surveillance of vaccine safety : A system to detect early signs of adverse events

Background: There currently are no population-based systems in the United States to rapidly detect adverse events after newly introduced vaccines. To evaluate the feasibility of developing such systems, we used 5 years of data from 4 health maintenance organizations within the Centers for Disease Control and Prevention (CDC) Vaccine Safety Datalink. Methods: Within every year, each weeks vaccinated children were followed for 4 weeks, and rates of adverse events were compared with rates among children of similar ages before the introduction of the new vaccine. We assessed risks for intussusception after rotavirus vaccination and risks for fever, seizures, and other neurologic adverse events after the change from whole cell diphtheria-tetanus-pertussis (DTPw) to acellular DTP vaccine (DTPa). We used sequential probability ratio testing, adjusted for age, sex, calendar time, season, and HMO, and with a stopping value based on the probability of an adverse event under the null hypothesis and under a preset alternative hypothesis. Results: We detected an increase in intussusception after 2589 vaccine doses of rotavirus vaccine, about the same time initial reports of intussusception were made to the Vaccine Adverse Events Reporting System. Decreases in risk for fever, seizures, and other abnormal neurologic events became detectable within 12 weeks, 42 weeks, and 18 months, respectively, after the change from DTPw to DTPa. Conclusions: We conclude that it is feasible to develop systems for rapid and routine population-based assessments of new vaccine safety.

Near Real-Time Surveillance for Influenza Vaccine Safety: Proof-of-Concept in the Vaccine Safety Datalink Project

The emergence of pandemic H1N1 influenza in 2009 has prompted public health responses, including production and licensure of new influenza A (H1N1) 2009 monovalent vaccines. Safety monitoring is a critical component of vaccination programs. As proof-of-concept, the authors mimicked near real-time prospective surveillance for prespecified neurologic and allergic adverse events among enrollees in 8 medical care organizations (the Vaccine Safety Datalink Project) who received seasonal trivalent inactivated influenza vaccine during the 2005/06-2007/08 influenza seasons. In self-controlled case series analysis, the risk of adverse events in a prespecified exposure period following vaccination was compared with the risk in 1 control period for the same individual either before or after vaccination. In difference-in-difference analysis, the relative risk in exposed versus control periods each season was compared with the relative risk in previous seasons since 2000/01. The authors used Poisson-based analysis to compare the risk of Guillain-Barré syndrome following vaccination in each season with that in previous seasons. Maximized sequential probability ratio tests were used to adjust for repeated analyses on weekly data. With administration of 1,195,552 doses to children under age 18 years and 4,773,956 doses to adults, no elevated risk of adverse events was identified. Near real-time surveillance for selected adverse events can be implemented prospectively to rapidly assess seasonal and pandemic influenza vaccine safety.

Self-report compared to electronic medical record across eight adult vaccines: Do results vary by demographic factors?

Immunizations are crucial to the prevention of disease, thus, having an accurate measure of vaccination status for a population is an important guide in targeting prevention efforts. In order to comprehensively assess the validity of self-reported adult vaccination status for the eight most common adult vaccines we conducted a survey of vaccination receipt and compared it to the electronic medical record (EMR), which was used as the criterion standard, in a population of community-dwelling patients in a large healthcare system. In addition, we assessed whether validity varied by demographic factors. The vaccines included: pneumococcal (PPSV), influenza (Flu), tetanus diphtheria (Td), tetanus diphtheria pertussis (Tdap), Human Papilloma Virus (HPV), hepatitis A (HepA), hepatitis B (HepB) and herpes zoster (shingles). Telephone surveys were conducted with 11,760 individuals, ≥18, half with documented receipt of vaccination and half without. We measured sensitivity, specificity, positive and negative predictive value, net bias and over- and under-reporting of vaccination. Variation was found across vaccines, however, sensitivity and specificity did not vary substantially by either age or race/ethnicity. Sensitivity ranged between 63% for HepA to over 90% (tetanus, HPV, shingles and Flu). Hispanics were 2.7 times more likely to claim receipt of vaccination compared to whites. For PPSV and Flu those 65+ had low specificity compared to patients of younger ages while those in the youngest age group had lowest specificity for HepA and HepB. In addition to racial/ethnic differences, over-reporting was more frequent in those retired and those with household income less than

Risk of immune thrombocytopenic purpura after measles-mumps-rubella immunization in children.

75,000. Accurate information for vaccination surveillance is important to estimate progress toward vaccination coverage goals and ensure appropriate policy decisions and allocation of resources for public health. It was clear from our findings that EMR and self-report do not always agree. Finding approaches to improve both EMR data capture and patient awareness would be beneficial.

Adolescent primary care visit patterns.

BACKGROUND. The measles-mumps-rubella vaccine has been associated with immune thrombocytopenia purpura in 2 small studies. METHODS. By using the Vaccine Safety Datalink, we identified measles-mumps-rubella–vaccinated children aged 1 to 18. A case of immune thrombocytopenia purpura was defined as a patient with a platelet count of ≤50000/μL with clinical bleeding and normal red and white blood cell indices. The immune thrombocytopenia purpura incidence rates during exposed (42 days after vaccination) and unexposed time periods were determined. A retrospective cohort of vaccinated children was used to determine incident rate ratios for children aged 1 to 18 years, 12 to 23 months, and 12 to 15 months. RESULTS. A total of 1036689 children received 1107814 measles-mumps-rubella vaccinations; there were 259 confirmed patients with immune thrombocytopenia purpura. Because only 5 exposed cases occurred after age 2, analyses were limited to children aged 12 to 23 months. Exposed patients aged 12 to 23 months had lower median platelet counts than those who were unexposed and had similar median duration of illness (11 vs 10 days). The incident rate ratio was highest for children aged 12 to 15 months at 7.10. The incident rate ratio for boys aged 12 to 15 months was 14.59, and the incident rate ratio for girls in the same age group was 3.22. Seventy-six percent of immune thrombocytopenia purpura cases in children aged 12 to 23 months were attributable to measles-mumps-rubella vaccination. This vaccine causes 1 case of immune thrombocytopenia purpura per every 40000 doses. CONCLUSION. Measles-mumps-rubella vaccine that is given in the second year of life is associated with an increased risk of immune thrombocytopenia purpura.

H1N1 and Seasonal Influenza Vaccine Safety in the Vaccine Safety Datalink Project

PURPOSE Many clinical preventive care services are recommended for adolescents. Little is known about whether most adolescents have a sufficient number of preventive care services visits over time to receive those services. We wanted to measure how frequently adolescents who are insured either through private insurance or government programs have preventive vs nonpreventive care visits. METHODS We conducted a retrospective descriptive analysis based on claims data from a large health plan in Minnesota with about 700,000 members. All study patients were aged 11 to 18 years between January 1, 1998, and December 31, 2007. Our outcome measure was rates of preventive and nonpreventive care visits. RESULTS One-third of adolescents with 4 or more years of continuous enrollment had no preventive care visits from age 13 through 17 years, and another 40% had only a single such visit. Nonpreventive care visits were more frequent in all age-groups, averaging about 1 per year at age 11 years, climbing to about 1.5 per year at age 17 years. Differences in rates between government insurance and commercial insurance were small. In older adolescence, girls had more preventive care visits and more nonpreventive care visits than did boys. CONCLUSIONS Most adolescents come in infrequently for preventive care visits but more often for nonpreventive care visits. We recommend using the same approach in adolescence for preventive care that is being used in adults: the no-missed-opportunities paradigm. All visits by adolescents should be viewed as an opportunity to provide preventive care services, and systems should be set up to make that possible, even in busy practices with short encounters with a clinician.

Recent Trends in Outpatient Antibiotic Use in Children

BACKGROUND The emergence of pandemic H1N1 influenza virus in early 2009 prompted the rapid licensure and use of H1N1 monovalent inactivated (MIV) and live, attenuated (LAMV) vaccines separate from seasonal trivalent inactivated (TIV) and live, attenuated (LAIV) influenza vaccines. A robust influenza immunization program in the U.S. requires ongoing monitoring of potential adverse events associated with vaccination. PURPOSE To prospectively conduct safety monitoring of H1N1 and seasonal influenza vaccines during the 2009-2010 season. METHODS The Vaccine Safety Datalink (VSD) Project monitors ∼9.2 million members in eight U.S. medical care organizations. Electronic data on vaccines and pre-specified adverse events were updated and analyzed weekly for signal detection from November 2009 to April 2010 using either a self-controlled design or a current versus historical comparison. Statistical signals were further evaluated using alternative approaches to identify temporal clusters and to control for time-varying confounders. RESULTS As of May 1, 2010, a total of 1,345,663 MIV, 267,715 LAMV, 2,741,150 TIV, and 157,838 LAIV doses were administered in VSD. No significant associations were noted during sequential analyses for Guillain-Barré syndrome, most other neurologic outcomes, and allergic and cardiac events. For MIV, a statistical signal was observed for Bells palsy for adults aged ≥25 years on March 31, 2010, using the self-controlled approach. Subsequent analyses revealed no significant temporal cluster. Case-centered logistic regression adjusting for seasonality demonstrated an OR for Bells palsy of 1.26 (95% CI=0.97, 1.63). CONCLUSIONS No major safety problems following H1N1 or seasonal influenza vaccines were detected in the 2009-2010 season in weekly sequential analyses. Seasonality likely contributed to the Bells palsy signal following MIV. Prospective safety monitoring followed by rigorous signal refinement is critical to inform decision-making by regulatory and public health agencies.