Jennifer C. Nelson

The U.S. Food and Drug Administration's Mini‐Sentinel program: status and direction

The Mini‐Sentinel is a pilot program that is developing methods, tools, resources, policies, and procedures to facilitate the use of routinely collected electronic healthcare data to perform active surveillance of the safety of marketed medical products, including drugs, biologics, and medical devices. The U.S. Food and Drug Administration (FDA) initiated the program in 2009 as part of its Sentinel Initiative, in response to a Congressional mandate in the FDA Amendments Act of 2007.

Prevention of relapse in women who quit smoking during pregnancy.

OBJECTIVES This study is an evaluation of relapse prevention interventions for smokers who quit during pregnancy. METHODS Pregnant smokers at 2 managed care organizations were randomized to receive a self-help booklet only, prepartum relapse prevention, or prepartum and postpartum relapse prevention. Follow-up surveys were conducted at 28 weeks of pregnancy and at 8 weeks, 6 months, and 12 months postpartum. RESULTS The pre/post intervention delayed but did not prevent postpartum relapse to smoking. Prevalent abstinence was significantly greater for the pre/post intervention group than for the other groups at 8 weeks (booklet group, 30%; prepartum group, 35%; pre/post group, 39%; P = .02 [different superscripts denote differences at P < .05]) and at 6 months (booklet group, 26%, prepartum group, 24%; pre/post group, 33%; P = .04) postpartum. A nonsignificant reduction in relapse among the pre/post group contributed to differences in prevalent abstinence. There was no difference between the groups in prevalent abstinence at 12 months postpartum. CONCLUSIONS Relapse prevention interventions may need to be increased in duration and potency to prevent post-partum relapse.

The test-negative design for estimating influenza vaccine effectiveness

OBJECTIVE The test-negative design has emerged in recent years as the preferred method for estimating influenza vaccine effectiveness (VE) in observational studies. However, the methodologic basis of this design has not been formally developed. METHODS In this paper we develop the rationale and underlying assumptions of the test-negative study. Under the test-negative design for influenza VE, study subjects are all persons who seek care for an acute respiratory illness (ARI). All subjects are tested for influenza infection. Influenza VE is estimated from the ratio of the odds of vaccination among subjects testing positive for influenza to the odds of vaccination among subjects testing negative. RESULTS With the assumptions that (a) the distribution of non-influenza causes of ARI does not vary by influenza vaccination status, and (b) VE does not vary by health care-seeking behavior, the VE estimate from the sample can generalized to the full source population that gave rise to the study sample. Based on our derivation of this design, we show that test-negative studies of influenza VE can produce biased VE estimates if they include persons seeking care for ARI when influenza is not circulating or do not adjust for calendar time. CONCLUSIONS The test-negative design is less susceptible to bias due to misclassification of infection and to confounding by health care-seeking behavior, relative to traditional case-control or cohort studies. The cost of the test-negative design is the additional, difficult-to-test assumptions that incidence of non-influenza respiratory infections is similar between vaccinated and unvaccinated groups within any stratum of care-seeking behavior, and that influenza VE does not vary across care-seeking strata.

Differences in preconceptional and prenatal behaviors in women with intended and unintended pregnancies.

OBJECTIVES This study examined whether pregnancy intention was associated with cigarette smoking, alcohol drinking, use of vitamins, and consumption of caffeinated drinks prior to pregnancy and in early pregnancy. METHODS Data from a telephone survey of 7174 pregnant women were analyzed. RESULTS In comparison with women whose pregnancies were intended, women with unintended pregnancies were more likely to report cigarette smoking and less likely to report daily vitamin use. Women with unintended pregnancies were also less likely to decrease consumption of caffeinated beverages or increase daily vitamin use. CONCLUSIONS Pregnancy intention was associated with health behaviors, prior to pregnancy and in early pregnancy, that may influence pregnancy course and birth outcomes.

Influenza vaccination and risk of community-acquired pneumonia in immunocompetent elderly people: a population-based, nested case-control study

BACKGROUND Pneumonia is a common complication of influenza infection in elderly individuals and could therefore potentially be prevented by influenza vaccination. In studies with data from administrative sources, vaccinated elderly people had a reduced risk of admission for pneumonia compared with unvaccinated seniors; however, these findings could have been biased by underlying differences in health between the groups. Furthermore, since most individuals with pneumonia are not treated in hospital, such studies should include both outpatient and inpatient events. We therefore assessed whether influenza vaccination is associated with a reduced risk of community-acquired pneumonia in immunocompetent elderly people after controlling for health status indicators. METHODS We did a population-based, nested case-control study in immunocompetent elderly people aged 65-94 years (cases and controls) enrolled in Group Health (a health maintenance organisation) during the 2000, 2001, and 2002 preinfluenza periods and influenza seasons. Cases were individuals with an episode of outpatient or inpatient community-acquired pneumonia (validated by review of medical records or chest radiograph reports). We randomly selected two age-matched and sex-matched controls for each case. The exposure of interest was influenza vaccination. We reviewed medical records to define potential confounders, including smoking history, presence and severity of lung and heart disease, and frailty indicators. FINDINGS 1173 cases and 2346 controls were included in the study. After we adjusted for the presence and severity of comorbidities, as defined by chart review, influenza vaccination was not associated with a reduced risk of community-acquired pneumonia (odds ratio 0.92, 95% CI 0.77-1.10) during the influenza season. INTERPRETATION The effect of influenza vaccination on the risk of pneumonia in elderly people during influenza seasons might be less than previously estimated. FUNDING Group Health Center for Health Studies internal funds and Group Health Community Foundation fellowship grant.

PARTNER SMOKING STATUS AND PREGNANT SMOKER'S PERCEPTIONS OF SUPPORT FOR AND LIKELIHOOD OF SMOKING CESSATION

Perceptions of support for cessation of smoking during pregnancy, likelihood of quitting, and partner smoking status were explored in a sample of 688 pregnant smokers (372 baseline smokers and 316 baseline quitters). Women with nonsmoking partners were significantly more likely to be baseline quitters than women with partners who smoked. Baseline quitters reported significantly more positive support from their partners than did continuing smokers (p = .02). Neither partner smoking status nor partner support at baseline was associated with cessation or relapse later in pregnancy. Women reported greater support, both positive and negative, from nonsmoking partners than from partners who smoked (p = .001). Among partner smokers, those who were trying to quit were perceived to be particularly supportive. Cessation interventions for expectant fathers may increase pregnant womens success at quitting.

Immunogenicity and Reactogenicity of 1 versus 2 Doses of Trivalent Inactivated Influenza Vaccine in Vaccine-Naive 5–8-Year-Old Children

BACKGROUND Two doses of trivalent inactivated influenza vaccine (TIV) are recommended for children <9 years old receiving vaccine for the first time, but compliance is suboptimal. This study assessed the need for a second dose of TIV in this age group. METHODS In this prospective, open-label study, 232 influenza vaccine-naive 5-8-year-olds enrolled in a health maintenance organization received 2 doses of TIV in fall 2004. Serum for antibody titer measurement was obtained at 3 time points (n = 222). Parents completed diaries for 5 days. RESULTS Both doses of vaccine were well tolerated. The strongest predictor of a protective antibody response (> or =1 : 40) after 1 dose of TIV was baseline seropositive status. In multivariate analysis adjusting for age, sex, and baseline serostatus, the proportion of children with protective antibody responses was significantly higher after 2 doses than after 1 dose of TIV for each antigen (P < .001, for A/H1N1; P = .01, for A/H3N2; P < .001, for B). Age and sex were not independently predictive of a protective antibody response. Over one-third of children had antibody responses <1:40 for the type B vaccine component, even after 2 doses. CONCLUSIONS The present study supports the need for 2 doses of TIV in 5-8-year-olds receiving TIV for the first time. Efforts to increase compliance with the 2-dose recommendation are warranted.

Impact of the introduction of pneumococcal conjugate vaccine on rates of community acquired pneumonia in children and adults.

Pneumococcal conjugate vaccine use among young children has led to significant declines in invasive pneumococcal disease in the United States, but the impact on community-acquired pneumonia is unknown. We conducted population-based pneumonia surveillance among 794,282 Group Health members before and after infant vaccine introduction in 2000. We presumptively identified pneumonia episodes using diagnosis codes assigned to medical encounters and confirmed 17,513 outpatient and 6318 hospitalized events by reviewing chest radiograph reports or hospitalization records. There was evidence for a decline in rates of both outpatient and hospitalized pneumonia in children less than 1 year of age following vaccine introduction but there were no consistent reductions in pneumonia rates among older children and adults.

Stress, depressive symptoms, and smoking cessation among pregnant women

Perceived stress and depressive symptoms were examined as correlates and predictors of smoking cessation during pregnancy in a sample of 819 pregnant smokers (454 baseline smokers and 365 baseline quitters). Women who quit early in pregnancy had lower levels of stress and depressive symptoms than baseline smokers. Adjusting for level of addiction and other demographic factors related to stress and depressive symptoms eliminated the significant association between depressive symptoms and smoking cessation. Lower levels of stress and depressive symptoms were not predictive of cessation in later pregnancy. Prenatal healthcare providers should continue to assess level of addiction and provide targeted intensive cessation interventions. Interventions that reduce stress and depression may also be of benefit to women who are continuing smokers in early pregnancy.

Metabolic syndrome, diabetes, and incidence and progression of coronary calcium: the Multiethnic Study of Atherosclerosis study.

OBJECTIVES This study sought to examine and compare the incidence and progression of coronary artery calcium (CAC) among persons with metabolic syndrome (MetS) and diabetes mellitus (DM) versus those with neither condition. BACKGROUND MetS and DM are associated with subclinical atherosclerosis as evidenced by CAC. METHODS The MESA (Multiethnic Study of Atherosclerosis) included 6,814 African American, Asian, Caucasian, and Hispanic adults 45 to 84 years of age, who were free of cardiovascular disease at baseline. Of these, 5,662 subjects (51% women, mean age 61.0 ± 10.3 years) received baseline and follow-up (mean 2.4 years) cardiac computed tomography scans. We compared the incidence of CAC in 2,927 subjects without CAC at baseline and progression of CAC in 2,735 subjects with CAC at baseline in those with MetS without DM (25.2%), DM without MetS (3.5%), or both DM and MetS (9.0%) to incidence and progression in subjects with neither MetS nor DM (58%). Progression of CAC was also examined in relation to coronary heart disease events over an additional 4.9 years. RESULTS Relative to those with neither MetS nor DM, adjusted relative risks (95% confidence intervals [CI]) for incident CAC were 1.7 (95% CI: 1.4 to 2.0), 1.9 (95% CI: 1.4 to 2.4), and 1.8 (95% CI: 1.4 to 2.2) (all p < 0.01), and absolute differences in mean progression (volume score) were 7.8 (95% CI: 4.0 to 11.6; p < 0.01), 11.6 (95% CI: 2.7 to 20.5; p < 0.05), and 22.6 (95% CI: 17.2 to 27.9; p < 0.01) for those with MetS without DM, DM without MetS, and both DM and MetS, respectively. Similar findings were seen in analysis using Agatston calcium score. In addition, progression predicted coronary heart disease events in those with MetS without DM (adjusted hazard ratio: 4.1, 95% CI: 2.0 to 8.5, p < 0.01) and DM (adjusted hazard ratio: 4.9 [95% CI: 1.3 to 18.4], p < 0.05) among those in the highest tertile of CAC increase versus no increase. CONCLUSIONS Individuals with MetS and DM have a greater incidence and absolute progression of CAC compared with individuals without these conditions, with progression also predicting coronary heart disease events in those with MetS and DM.