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The self-controlled case series (SCCS) and the matched cohort are two frequently used study designs to adjust for known and unknown con- founding effects in epidemiological studies. Count data arising from these two designs may not be independent. While conditional Poisson regres- sion models have been used to take into account the dependence of such data, these models have not been available in some standard statistical soft- ware packages (e.g., SAS). This article demonstrates 1) the relationship of the likelihood function and parameter estimation between the conditional Poisson regression models and Cox's proportional hazard models in SCCS and matched cohort studies; 2) that it is possible to fit conditional Pois- son regression models with procedures (e.g., PHREG in SAS) using Cox's partial likelihood model. We tested both conditional Poisson likelihood and Cox's partial likelihood models on data from studies using either SCCS or a matched cohort design. For the SCCS study, we fitted both parametric and semi-parametric models to model age effects, and described a simple way to apply the parametric and complex semi-parametric analysis to case series data.

Summary: Background: Paediatric vaccination against influenza can result in indirect protection, by reducing transmission to their unvaccinated contacts. We investigated whether influenza vaccination of children would protect them and their household members in a resource-limited setting. Methods: We did a cluster-randomised, blinded, controlled study in three villages in India. Clusters were defined as households (ie, dwellings that shared a courtyard), and children aged 6 months to 10 years were eligible for vaccination as and when they became age-eligible throughout the study. Households were randomly assigned (1:1) by a computer-based system to intramuscular trivalent inactivated influenza vaccine (IIV3) or a control of inactivated poliovirus vaccine (IPV) in the beginning of the study; vaccination occurred once a year for 3 years. The primary efficacy outcome was laboratory-confirmed influenza in a vaccinated child with febrile acute respiratory illness, analysed in the modified intention-to-treat population (ie, children who received at least one dose of vaccine, were under surveillance, and had not an influenza infection within 15 days of last vaccine dose). The secondary outcome for indirect effectiveness (surveillance study) was febrile acute respiratory illness in an unvaccinated household member of a vaccine study participant. Data from each year (year 1: November, 2009, to October, 2010; year 2: October, 2010, to October, 2011; and year 3: October, 2011, to May, 2012) were analysed separately. Safety was analysed among all participants who were vaccinated with at least one dose of the vaccine. This trial is registered with ClinicalTrials.gov, number NCT00934245. Findings: Between Nov 1, 2009, to May 1, 2012, we enrolled 3208 households, of which 1959 had vaccine-eligible children. 1010 households were assigned to IIV3 and 949 households were assigned to IPV. In 3 years, we vaccinated 4345 children (2132 with IIV3 and 2213 with IPV) from 1868 households (968 with IIV3 and 900 with IPV) with 10 813 unvaccinated household contacts. In year 1, influenza virus was detected in 151 (10%) of 1572 IIV3 recipients and 206 (13%) of 1633 of IPV recipients (total IIV3 vaccine efficacy 25·6% [95% CI 6·8–40·6]; p=0·010). In year 2, 105 (6%) of 1705 IIV3 recipients and 182 (10%) of 1814 IPV recipients had influenza (vaccine efficacy 41·0% [24·1–54·1]; p

The West Africa Ebola epidemic stimulated rapid implementation of Ebola vaccine trials in the 3 highly affected countries. In Sierra Leone, we studied the recombinant vesicular stomatitis virus Ebola vaccine (rVSV∆G-ZEBOV-GP) safety and efficacy. The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) was a randomized, unblinded Phase 2/3 trial with phased vaccine introduction, no placebo, and concurrent evaluation of vaccine safety and efficacy. Healthcare and frontline response workers in 5 districts were randomized to immediate or deferred (18–24 weeks later) vaccination and followed for 6 months postvaccination. We enrolled 8651 participants from April through August 2015; 7998 were vaccinated. No participants developed Ebola virus disease so an efficacy assessment was not possible. Overall, 132 (1.5%) participants experienced serious adverse events (SAEs); none were vaccine-related. In a detailed safety substudy (N = 436), vaccinated participants reported significantly more systemic adverse events (AEs) within 7 days than unvaccinated participants including fever higher than 38°C (20.5% vs 3.9%), headache (71.2% vs 22.1%), fatigue (50.7% vs 10.4%), and joint pain (31.7% vs 6.5%); most AEs were mild to moderate severity and resolved within 5 days. During days 5-28, vaccinated participants more commonly reported joint pain (17.0% vs 4.8%) and rash (7.8% vs 1.7%) (P

With influenza vaccination rates in the United States recently exceeding 45% of the population, it is important to understand the impact that vaccination is having on influenza transmission. In this study, we used a Bayesian modeling approach, combined with a simple dynamical model of influenza transmission, to estimate this impact. The combined framework synthesized evidence from a range of data sources relating to influenza transmission and vaccination in the United States. We found that, for seasonal epidemics, the number of infections averted ranged from 9.6 million in the 2006-2007 season (95% credible interval (CI): 8.7, 10.9) to 37.2 million (95% CI: 34.1, 39.6) in the 2012-2013 season. Expressed in relative terms, the proportion averted ranged from 20.8% (95% CI: 16.8, 24.3) of potential infections in the 2011-2012 season to 47.5% (95% CI: 43.7, 50.8) in the 2008-2009 season. The percentage averted was only 1.04% (95% CI: 0.15, 3.2) for the 2009 H1N1 pandemic, owing to the late timing of the vaccination program in relation to the pandemic in the Northern hemisphere. In the future, further vaccination coverage, as well as improved influenza vaccines (especially those offering better protection in the elderly), could have an even stronger effect on annual influenza epidemics.

Background Live attenuated influenza vaccine (LAIV) is safe in healthy children ⩾2 years. The original clinical trials excluded individuals with underlying conditions; however, post-marketing data suggest LAIV may be safe for these populations. Methods We analyzed MarketScan Commercial Claims Databases from 2010 to 2012 to describe hospitalizations within 14 days of vaccination among LAIV recipients. We evaluated LAIV recipients aged 2–18 years and defined underlying conditions by presence of inpatient or outpatient ICD-9 code during the previous calendar year. We excluded asthma and immunocompromising conditions. We defined risk windows as 1–7 days and 8–14 days after vaccination; the control period was 12–4 days prior to and 15–23 days after vaccination. We conducted a self-controlled case series analysis using a conditional Poisson regression model to estimate incidence-rate ratios (IRR). Results 1,216,123 children aged 2–18 years received LAIV from 2010 to 2012. 634 children met our inclusion criteria and were hospitalized during the observation period (12 days prior to vaccination to 23 days after vaccination). Of those hospitalized, 72 (11.4%) had non-asthma, non-immunocompromising underlying conditions. Children with non-asthma, non-immunocompromising underlying conditions had an all-cause hospitalization IRR of 1.1 (95% CI 0.6–2.0, p = 0.83) in the 1–7 day risk period and 0.9 (95% CI 0.4–1.7, p = 0.67) in the 8–14 day risk period. Children with no underlying conditions had an all-cause hospitalization IRR of 0.9 (0.8–1.2, p = 0.60) in the 1–7 day risk period and 1.1 (95% CI 0.9–1.3, p = 0.53) in the 8–14 day risk period. There were no differences in all-cause hospitalization risk in individuals with non-asthma, non-immunocompromising underlying conditions compared to those without underlying conditions in the 1–7 day (p = 0.88) or 8–14 day (p = 0.24) risk period. Conclusions We found no evidence of differences in post-LAIV hospitalization risk among children with non-asthma, non-immunocompromising underlying conditions compared to healthy children.

Oseltamivir reduces symptom duration among children with uncomplicated influenza, but few data exist on treatment efficacy and tolerability among hospitalized children, particularly among infants aged1 year. We evaluated tolerability and efficacy of oseltamivir treatment of children aged 0-9 years hospitalized with influenza.We conducted a double-blind, randomized, placebo-controlled trial at tertiary care hospitals in El Salvador and Panama. Primary outcomes were length of hospitalization and increased work of breathing. Children were eligible if hospitalized7 days after symptom onset with cough or sore throat plus tachypnea. Children were randomized 1:1 to receive oseltamivir or placebo; had swabs collected at enrollment for influenza RT-PCR testing; were assessed at enrollment and every 12 h for work of breathing; and were followed for adverse events through 7 days after discharge. Analyses were intention-to-treat.Overall, 683 children were randomized (oseltamivir, n = 341, placebo n = 342). Fifty-three percent were aged1 year and 30 had influenza (oseltamivir, n = 19; placebo, n = 11). The study was terminated early after enrollment of 21% of the sample size due to lower than anticipated participant accrual. Using Kaplan-Meier analysis, there was no significant difference in median length of hospitalization (3 days, IQR 2-4 vs. 5 days, IQR 3-7, p = 0.22) and increased work of breathing (36 h, IQR 24-72 vs. 96 h, IQR 13-108, p = 0.14) between oseltamivir versus placebo recipients. There was no difference in adverse events between groups.Oseltamivir treatment was well tolerated among hospitalized children, including among infants aged1 year.

Background Influenza viruses gradually accumulate point mutations, reducing the effectiveness of prior immune protection. Methods Children aged 9-14 years received 2010-2011 trivalent inactivated influenza vaccine (TIV). Vaccination history, hemagglutination-inhibition (HI) titers, and cell-mediated immune responses were assessed to investigate the cross-reactivity with past and future influenza virus strains. Results 2010-2011 TIV induced significant T-cell responses and HI titers of ≥160, with a fold-rise of ≥4 and titers of ≥100 maintained for >7 months in the majority of children. Pre-existing memory B cells in these children differentiated quickly to antibody-secreting cells to the new vaccine antigens. Children vaccinated in the previous year maintained high HI titers well into 2010, demonstrating elevated HI titers against A/Perth/16/2009, the future (in 2010-2011) H3N2 component. Prior vaccination enhanced CD8+ T-cell responses to A/Perth/16/2009. Children vaccinated with the prior 2009-2010 seasonal vaccine also demonstrated higher preexisting levels of interferon γ-secreting CD4+CD69+ T cells to 2009 pandemic influenza A(H1N1). Children previously vaccinated with 2009-2010 seasonal influenza vaccine also showed greater expansion of tumor necrosis factor α-secreting CD8+CD69+ T cells to 2009 pandemic influenza A(H1N1) upon vaccination in the 2010-2011 season than those who were not previously vaccinated. Conclusions Seasonal influenza viruses continuously drift, which allows them to circumvent protective immunity, but conserved epitopes provide immunological cross-reactivity in children through either vaccination directly or through prime/boost in the prior influenza season.

Background We describe the impact of early initiation of influenza antiviral treatment among pregnant women hospitalized with laboratory-confirmed influenza during the 2010-2014 influenza seasons. Methods Severe influenza was defined as illness with ≥1 of the following: intensive care unit admission, need for mechanical ventilation, respiratory failure, pulmonary embolism, sepsis, or death. Within severity stratum, we used parametric survival analysis to compare length of stay by timing of antiviral treatment, adjusting for underlying conditions, influenza vaccination, and pregnancy trimester. Results Among 865 pregnant women, the median age was 27 years (interquartile range [IQR], 23-31 years). Most (68%) were healthy, and 85% received antiviral treatment. Sixty-three women (7%) had severe influenza, and 4 died. Severity was associated with preterm delivery and fetal loss. Women with severe influenza were less likely to be vaccinated than those without severe influenza (14% vs 26%; P = .03). Among women treated with antivirals ≤2 days versus those treated >2 days from illness onset, the median length of stay was 2.2 days (interquartile range [IQR], 0.9-5.8 days; n = 8) versus 7.8 days (IQR, 3.0-20.6 days; n = 7), respectively, for severe influenza (P = .03) and 2.4 days (IQR, 2.3-2.5 days; n = 153) versus 3.1 days (IQR, 2.8-3.5 days; n = 62), respectively, for nonsevere influenza (P Conclusions Early initiation of influenza antiviral treatment to pregnant women hospitalized with influenza may reduce the length of stay, especially among those with severe influenza. Influenza during pregnancy is associated with maternal and infant morbidity, and annual influenza vaccination is warranted.

Some studies reported an increased risk of Guillain-Barré syndrome (GBS) within six weeks of influenza vaccination. It has also been suggested that this finding could have been confounded by influenza illnesses. We explored the complex relationship between influenza illness, influenza vaccination, and GBS, from an ecologic perspective using nationally representative data. We also studied seasonal patterns for GBS hospitalizations. Monthly hospitalization data (2000-2009) for GBS, and pneumonia and influenza (PI) in the Nationwide Inpatient Sample were included. Seasonal influenza vaccination coverage for 2004-2005 through the 2008-2009 influenza seasons (August-May) was estimated from the National Health Interview Survey data. GBS seasonality was determined using Poisson regression. GBS and PI temporal clusters were identified using scan statistics. The association between PI and GBS hospitalizations in the same month (concurrent) or in the following month (lagged) were determined using negative binomial regression. Vaccine coverage increased over the years (from 19.7% during 2004-2005 to 35.5% during 2008-2009 season) but GBS hospitalization did not follow a similar pattern. Overall, a significant correlation between monthly PI and GBS hospitalizations was observed (Spearman's correlation coefficient=0.7016, p0.0001). A significant (p=0.001) cluster of PI hospitalizations during December 2004-March 2005 overlapped a significant (p=0.001) cluster of GBS hospitalizations during January 2005-February 2005. After accounting for effects of monthly vaccine coverage and age, PI hospitalization was significantly associated (p0.0001) with GBS hospitalization in the concurrent month but not with GBS hospitalization in the following month. Monthly vaccine coverage was not associated with GBS hospitalization in adjusted models (both concurrent and lagged). GBS hospitalizations demonstrated a seasonal pattern with winter months having higher rates compared to the month of June. PI hospitalization rates were significantly correlated with hospitalization rates for GBS. Vaccine coverage did not significantly affect the rates of GBS hospitalization at the population level.

Background Pneumonia poses a significant burden to the U.S. health-care system. However, there are few data focusing on severe pneumonia, particularly cases of pneumonia associated with specialized care in intensive care units (ICU). Methods We used administrative and electronic medical record data from six integrated health care systems to estimate rates of pneumonia hospitalizations with ICU admissions among adults during 2006 through 2010. Pneumonia hospitalization was defined as either a primary discharge diagnosis of pneumonia or a primary discharge diagnosis of sepsis or respiratory failure with a secondary diagnosis of pneumonia in administrative data. ICU admissions were collected from internal electronic medical records from each system. Comorbidities were identified by ICD-9-CM codes coded during the current pneumonia hospitalization, as well as during medical visits that occurred during the year prior to the date of admission. Results We identified 119,537 adult hospitalizations meeting our definition for pneumonia. Approximately 19% of adult pneumonia hospitalizations had an ICU admission. The rate of pneumonia hospitalizations requiring ICU admission during the study period was 76 per 100,000 population/year; rates increased for each age-group with the highest rates among adults aged ≥85 years. Having a co-morbidity approximately doubled the risk of ICU admission in all age-groups. Conclusions Our study indicates a significant burden of pneumonia hospitalizations with an ICU admission among adults in our cohort during 2006 through 2010, especially older age-groups and persons with underlying medical conditions. These findings reinforce current strategies aimed to prevent pneumonia among adults. Electronic supplementary material The online version of this article (10.1186/s12890-017-0552-x) contains supplementary material, which is available to authorized users.

BACKGROUND AND OBJECTIVES: Surveillance for laboratory-confirmed influenza-associated pediatric deaths since 2004 has shown that most deaths occur in unvaccinated children. We assessed whether influenza vaccination reduced the risk of influenza-associated death in children and adolescents. METHODS: We conducted a case–cohort analysis comparing vaccination uptake among laboratory-confirmed influenza-associated pediatric deaths with estimated vaccination coverage among pediatric cohorts in the United States. Case vaccination and high-risk status were determined by case investigation. Influenza vaccination coverage estimates were obtained from national survey data or a national insurance claims database. We estimated odds ratios from logistic regression comparing odds of vaccination among cases with odds of vaccination in comparison cohorts. We used Bayesian methods to compute 95% credible intervals (CIs) for vaccine effectiveness (VE), calculated as (1 − odds ratio) × 100. RESULTS: From July 2010 through June 2014, 358 laboratory-confirmed influenza-associated pediatric deaths were reported among children aged 6 months through 17 years. Vaccination status was determined for 291 deaths; 75 (26%) received vaccine before illness onset. Average vaccination coverage in survey cohorts was 48%. Overall VE against death was 65% (95% CI, 54% to 74%). Among 153 deaths in children with underlying high-risk medical conditions, 47 (31%) were vaccinated. VE among children with high-risk conditions was 51% (95% CI, 31% to 67%), compared with 65% (95% CI, 47% to 78%) among children without high-risk conditions. CONCLUSIONS: Influenza vaccination was associated with reduced risk of laboratory-confirmed influenza-associated pediatric death. Increasing influenza vaccination could prevent influenza-associated deaths among children and adolescents.

One to 4 million cases of community-acquired pneumonia (CAP) occur annually in the United States, resulting in 600,000 hospitalizations and 45,000 deaths. Influenza infection facilitates secondary bacterial infections, and influenza vaccination may prevent CAP directly by preventing influenza pneumonia or indirectly by preventing secondary bacterial CAP.We investigated how influenza vaccination could affect incidence of CAP using deterministic probability and stochastic simulation models. The models included likely influential factors, including vaccine effectiveness (VE) against influenza, rates of influenza in the unvaccinated, vaccination coverage, and the relative risk (RR) of pneumonia, given influenza infection. To estimate effectiveness of influenza vaccine against CAP, we assumed mean VE against influenza of 55% and vaccine coverage of 38%.Given our baseline parameters, influenza vaccine had a mean effectiveness against CAP of 7% (95% confidence interval = 0-25%). Effectiveness of influenza vaccine against CAP increased as its effectiveness against influenza increased, as RR of pneumonia after influenza infection increased, and as rates of influenza among unvaccinated persons increased.No matter how effective vaccine may be in preventing influenza infection, it is only modestly effective at preventing CAP. Because of the large annual burden of CAP, a vaccine that is only moderately effective in preventing influenza infection has the potential to prevent a substantial number of CAP cases. This modeling approach may be useful for planning influenza vaccine-probe studies and evaluating the effectiveness of other interventions targeted against infections that manifest in nonspecific outcomes.

Background. In late October 2009, school-located pandemic vaccination was initiated in Maine before or concurrent with 2009 pandemic influenza A (H1N1) virus (pH1N1) peak activity. Methods. A case–control evaluation of 2009 H1N1 vaccine effectiveness was conducted in schools in Cumberland County, Maine. A case was a child who had an acute respiratory illness during 2 November–18 December 2009, and who tested positive for pH1N1 by real-time reverse-transcription polymerase chain reaction (rRTPCR). For each case, ≥4 event time-matched controls were sampled among classmates present in school during the study period who did not have an influenza-like illness. Vaccine effectiveness was calculated as (1 – adjusted odds ratio [aOR]) × 100%; aOR was estimated by using weighted logistic regression. Results. After adjusting for a diagnosis of asthma, 1 dose of 2009 H1N1 vaccine provided 69% protection (95% confidence interval (CI), 13–89) against rRT-PCR–confirmed H1N1 infection. Vaccine effectiveness estimates for live attenuated and inactivated vaccine were 81% (95% CI, −37 to 97), and 58% (95% CI: −39 to 87), respectively. Conclusions. One dose of monovalent pandemic vaccine provided substantial protection against pH1N1 infection among school-aged children.

Purpose The Centers for Disease Control and Prevention Emerging Infections Program implemented active, population-based surveillance for Guillain–Barre syndrome (GBS) following H1N1 vaccines in 10 states/metropolitan areas. We report additional analyses of these data using self-controlled methods, which avoid potential confounding from person-level factors and co-morbidities. Methods Surveillance officers identified GBS cases with symptom onset during October 2009–April 2010 and ascertained receipt of H1N1 vaccines. We calculated self-controlled relative risks by comparing the number of cases with onset during a risk interval 1–42 days after vaccination with cases with onset during fixed (days 43–84) or variable (days 43–end of study period) control intervals. We calculated attributable risks by applying statistically significant relative risks to an independent estimate of GBS incidence. Results Fifty-nine GBS cases received H1N1 vaccine with or without seasonal vaccine. The relative risk was 2.1 (95%CI 1.2, 3.5) by the variable-window and 3.0 (95%CI 1.4, 6.4) by the fixed-window analyses. The corresponding attributable risks per million doses administered were 1.5 (95%CI 0.3, 3.4) and 2.8 (95%CI 0.6, 7.4). Conclusions These attributable risks are similar to those of some previous formulations of seasonal influenza vaccine (about one to two cases per million doses administered), suggesting a low risk of GBS following the H1N1 vaccine that is not clearly higher than that of seasonal influenza vaccines. Published 2012. This article is a US Government work and is in the public domain in the USA.

During the 2007-08 influenza season, we reported an interim vaccine effectiveness (VE) estimate of 44% for preventing medically attended influenza. In this analysis we report results for the entire season and compare them with the interim estimate.Patients with feverishness, chills, or cough8 days duration were prospectively recruited over 10 weeks and tested for influenza by real-time reverse transcriptase PCR (rRT-PCR). Case-control analyses were performed using data from patients with rRT-PCR confirmed influenza (cases) and ill patients without influenza (test-negative controls). VE was estimated as 100×(1-adjusted odds ratio) in a logistic regression model adjusting for age, week, and high risk medical condition. A sample of influenza isolates was antigenically characterized.Influenza was detected by rRT-PCR in 865 (44%) of 1972 patients; 73% were type A and 27% were type B. VE was 37% (95% CI, 22-49%) overall and 44% (95% CI, 27-58%) among participants tested 0-3 days after illness onset. VE was 39% (95% CI, 2-62%) in children 6-59 months old and 37% (95% CI, -2% to 61%) in adults ≥50 years old. VE was 41% (95% CI, 24-53%) for influenza A and 31% (95% CI, 3-51%) for influenza B. All 24 characterized influenza A viruses were antigenically matched to the H3N2 vaccine strain, although 14 viruses exhibited mild antigenic drift. There was a lineage mismatch with the vaccine strain for all 39 characterized influenza B viruses.The 2007-08 influenza vaccine provided modest protection against medically attended influenza in this population. The interim estimate of VE after 17 days closely approximated the final season VE, supporting the potential use of interim VE estimates while influenza seasons are still in progress.

Background: In 1999, a US case-control study demonstrated a strong association between intussusception and a rotavirus vaccine (Rotashield). However, because most (87%) cases were not temporally associated with vaccination, we reanalyzed these data to assess risk factors for intussusception cases unrelated to Rotashield. Patients and Methods: Case-patients were infants with intussusception between November 1998 and June 1999. Controls were matched by age and hospital ofbirth. Sociodemographic and feeding practice data were collected through parent and provider interviews. Conditional logistic regression was used to identify risk factors for intussusception, controlling for exposure to Rotashield

Objectives. We performed a case–control study to determine if participants with herpes zoster had fewer contacts with persons with varicella or zoster, and with young children, to explore the hypothesis that exposure to persons with varicella zoster virus (VZV) results in “immune boosting.” Methods. Participants were patients of the multispecialty Marshfield Clinic in Wisconsin. We identified patients aged 40 to 79 years with a new diagnosis of zoster from August 2000 to July 2005. We frequency matched control participants to case participants for age. We confirmed diagnoses by chart review and assessed exposures by interview. Results. Interviews were completed by 633 of 902 eligible case participants (70.2%) and 655 of 1149 control participants (57.0%). The number of varicella contacts was not associated with zoster; there was no trend even at the highest exposure level (3 or more contacts). Similarly, there was no association with exposure to persons with zoster or to children, or with workplace exposures. Conclusions. Although exposure to VZV in our study was relatively low, the absence of a relationship with zoster reflects the uncertain influence of varicella circulation on zoster epidemiology.

OBJECTIVES. We assessed the validity of reported varicella history as a marker for varicella zoster virus immunity among unvaccinated persons 1 to 29 years of age, and we examined varicella disease characteristics associated with varicella zoster virus immunity among those reporting positive histories. METHODS. We conducted a cross-sectional study at 7 community-based sites in Philadelphia, Pennsylvania, between June 2004 and May 2006 and recruited 1476 participants 1 to 29 years of age who had not been vaccinated against varicella. Sensitivity, specificity, and positive predictive value were determined by comparing self-reported or parent-reported varicella histories from a standardized study interview with varicella zoster virus immunoglobulin G serological results for each participant. We performed multivariate logistic regression analyses to determine which disease characteristics best predicted seropositivity. RESULTS. The sensitivity of reported varicella history was highest (81%–89%) among participants ≥10 years of age, whereas specificity was highest among participants 1 to 4 years of age (99%) and ≥20 years (88%). Reported varicella history was highly predictive of seropositivity (>95%) only among participants ≥15 years of age. For participants 10 to 14 years of age, parental reports of a generalized itchy rash with 1 of the following were highly predictive of seropositivity: varicella transmission to another household member or being raised in a household with no other children. Among participants ≤9 years of age, no combination of disease characteristics was both highly predictive of seropositivity and common. CONCLUSIONS. The validity of reported varicella history varies according to age, and a reported history is no longer highly predictive of seropositivity among cohorts born since 1994 (participants ≤9 years of age). Universal varicella vaccination, regardless of history, for these children should be considered, as should simplified criteria for varicella zoster virus immunity among unvaccinated persons born before 1994.

Purpose To evaluate a possible association between influenza vaccination and four deaths and four serious illnesses among 114 recent influenza vaccinees in a long-term care facility (LTCF) and two deaths from a nearby physician's office. All had received vaccine from the same lot (Lot A). Methods Field investigation including (1) a retrospective cohort study among LTCF residents who received Lot A or other influenza vaccine, (2) review of medical records of cases of death or serious illness, (3) active surveillance of deaths among 1500 community based Lot A vaccinees and (4) laboratory testing of vaccine from available Lot A vials. Results Medical record reviews showed no common clinical syndrome or cause of death. Laboratory testing of Lot A samples revealed no evidence of tampering and no differences compared to an unrelated lot. The risk of death or hospitalization was not significantly different between persons who received Lot A versus a comparison lot, Lot B (incidence rate ratio (IRR) = 0.9, 95%CI = 0.3–3.3). Conclusions There was no clinical or biological evidence pointing to inherent vaccine safety issues, nor was there a detectable increased risk of death or hospitalization among persons vaccinated with Lot A. Lot specific clustering of adverse events (AEs) may reflect medical events causally unrelated to vaccination. Rapid investigations of potential AEs are important to ensure vaccine safety and to maintain public and healthcare provider confidence in vaccines. Copyright © 2009 John Wiley & Sons, Ltd.

BACKGROUND. In 1999, a previous rotavirus vaccine (RotaShield; Wyeth Laboratories, Marietta, PA) was withdrawn from the US market after postlicensure monitoring identified an association with intussusception. Although the new rotavirus vaccine (RotaTeq; Merck, West Point, PA) introduced in 2006 was not associated with intussusception in prelicensure trials, additional monitoring is important to ensure a complete safety profile. METHODS. We assessed intussusception reports after RotaTeq vaccination by using data from the Vaccine Adverse Event Reporting System and the Vaccine Safety Datalink, a cohort of children enrolled in managed care. Observed versus expected rate ratios were determined by using vaccine dose distribution data and Vaccine Safety Datalink background intussusception rates. RESULTS. Between February 1, 2006, and September 25, 2007, the Vaccine Adverse Event Reporting System received 160 intussusception reports after RotaTeq vaccination. With the assumptions that reporting completeness was 75% and that 75% of the distributed doses of RotaTeq were administered, the observed versus expected rate ratios were 0.53 and 0.91 for the 1–21 and 1–7 day interval after vaccination, respectively. In the Vaccine Safety Datalink, 3 intussusception cases occurred within 30 days after 111521 RotaTeq vaccinations, compared with 6 cases after 186722 non–RotaTeq vaccinations during the same period. If, like RotaShield, RotaTeq had a 37-fold increased risk of intussusception within 3 to 7 days after vaccination, then 8 intussusception cases would be expected within 3 to 7 days among the ∼84000 infants vaccinated with the first dose of RotaTeq in the Vaccine Safety Datalink (N = 49902) and the prelicensure trial (N = 34035) combined, whereas no cases have been observed. CONCLUSIONS. Available data do not indicate that RotaTeq is associated with intussusception. Although an intussusception risk similar in magnitude to that of RotaShield can be excluded, continued monitoring is necessary for complete assessment of the safety profile of RotaTeq.

Significant reductions in varicella incidence were reported from 1995 to 2000 in the varicella active surveillance sites of Antelope Valley (AV), California, and West Philadelphia (WP), Pennsylvania. We examined incidence rates, median age, and vaccination status of case patients for 1995-2005. Coverage data were from the National Immunization Survey. By 2005, coverage among children 19-35 months of age reached 92% (AV) and 94% (WP); 57% and 64% of case patients in AV and WP, respectively, were vaccinated; and varicella incidence declined by 89.8% in AV and 90.4% in WP. Incidence declined in all age groups, especially among children

Background Influenza causes substantial morbidity and annual vaccination is the most important prevention strategy. Accurately measuring vaccine effectiveness (VE) is difficult. The clinical syndrome most closely associated with influenza virus infection, influenza-like illness (ILI), is not specific. In addition, laboratory confirmation is infrequently done, and available rapid diagnostic tests are imperfect. The objective of this study was to estimate the joint impact of rapid diagnostic test sensitivity and specificity on VE for three types of study designs: a cohort study, a traditional case-control study, and a case-control study that used as controls individuals with ILI who tested negative for influenza virus infection. Methods We developed a mathematical model with five input parameters: true VE, attack rates (ARs) of influenza-ILI and non-influenza-ILI and the sensitivity and specificity of the diagnostic test. Results With imperfect specificity, estimates from all three designs tended to underestimate true VE, but were similar except if fairly extreme inputs were used. Only if test specificity was 95% or more or if influenza attack rates doubled that of background illness did the case-control method slightly overestimate VE. The case-control method usually produced the highest and most accurate estimates, followed by the test-negative design. The bias toward underestimating true VE introduced by low test specificity increased as the AR of influenza- relative to non-influenza-ILI decreases and, to a lesser degree, with lower test sensitivity. Conclusions Demonstration of a high influenza VE using tests with imperfect sensitivity and specificity should provide reassurance that the program has been effective in reducing influenza illnesses, assuming adequate control of confounding factors.

The introduction of universal varicella vaccination in 1995 has substantially reduced varicella-related morbidity and mortality in the United States. However, it remains unclear whether vaccine-induced immunity wanes over time, a condition that may result in increased susceptibility later in life, when the risk of serious complications may be greater than in childhood.We examined 10 years (1995 to 2004) of active surveillance data from a sentinel population of 350,000 subjects to determine whether the severity and incidence of breakthrough varicella (with an onset of rash42 days after vaccination) increased with the time since vaccination. We used multivariate logistic regression to adjust for the year of disease onset (calendar year) and the subject's age at both disease onset and vaccination.A total of 11,356 subjects were reported to have varicella during the surveillance period, of whom 1080 (9.5%) had breakthrough disease. Children between the ages of 8 and 12 years who had been vaccinated at least 5 years previously were significantly more likely to have moderate or severe disease than were those who had been vaccinated less than 5 years previously (risk ratio, 2.6; 95% confidence interval [CI], 1.2 to 5.8). The annual rate of breakthrough varicella significantly increased with the time since vaccination, from 1.6 cases per 1000 person-years (95% CI, 1.2 to 2.0) within 1 year after vaccination to 9.0 per 1000 person-years (95% CI, 6.9 to 11.7) at 5 years and 58.2 per 1000 person-years (95% CI, 36.0 to 94.0) at 9 years.A second dose of varicella vaccine, now recommended for all children, could improve protection from both primary vaccine failure and waning vaccine-induced immunity.

Objectives. Exposure to varicella zoster virus through close contact with people with chickenpox was suggested to boost specific immunity, reducing the risk of herpes zoster (HZ). Since the introduction of the varicella immunization program in the U.S. in 1995, varicella morbidity has decreased substantially. This article examines incidence and risk factors associated with self-reported HZ disease and whether exposure to chickenpox within the previous decade reduces the risk of shingles in this age group. Methods. In 2004, a national random-digit dial telephone survey was used to obtain information on self-reported HZ disease, demographic characteristics, and exposure to children with chickenpox in the past decade. National estimates of the incidence of shingles disease were calculated. Results. Incidence rate of self-reported HZ was 19 per 1,000 population per year. White individuals were 3.5 times more likely to report shingles than Hispanic individuals ( pConclusions. Incidence of HZ among individuals ≥65 years of age in the U.S. may be higher than previously described in the literature, with whites being at higher risk for the disease. Currently, the potential contribution of exposure to chickenpox as a mechanism for maintaining cell-mediated immunity against HZ may be limited to a small percentage of the population. Vaccination against HZ may represent the best means of decreasing this disease burden.

During the 2003-2004 influenza season, we conducted a case-control study of influenza vaccine effectiveness (VE) among Colorado residents aged 50-64 years. Cases (n=330) were identified from laboratory-confirmed influenza reports to the Colorado Department of Public Health and Environment (CDPHE). Controls (n=1055) were recruited by random-digit dial telephone survey. VE was 60% (43-72%) and 48% (21-66%) among those without and with high-risk medical conditions, respectively. VE was 90% (68-97%) and 36% (0-63%) against influenza-related hospitalization for persons without and with high-risk conditions, respectively.

Background. Influenza disproportionately impacts older adults while current vaccines have reduced effectiveness in the older population. Methods. We conducted a comprehensive evaluation of cellular and humoral immune responses of adults aged 50 years and older to the 2008–2009 seasonal trivalent inactivated influenza vaccine and assessed factors influencing vaccine response. Results. Vaccination increased hemagglutination inhibition and neutralizing antibody; however, 66.3% of subjects did not reach hemagglutination inhibition titers ≥ 40 for H1N1, compared with 22.5% for H3N2. Increasing age had a minor negative impact on antibody responses, whereas prevaccination titers were the best predictors of postvaccination antibody levels. Preexisting memory B cells declined with age, especially for H3N2. However, older adults still demonstrated a significant increase in antigen-specific IgG+ and IgA+ memory B cells postvaccination. Despite reduced frequency of preexisting memory B cells associated with advanced age, fold-rise in memory B cell frequency in subjects 60+ was comparable to subjects age 50–59. Conclusions. Older adults mounted statistically significant humoral and cell-mediated immune responses, but many failed to reach hemagglutination inhibition titers ≥40, especially for H1N1. Although age had a modest negative effect on vaccine responses, prevaccination titers were the best predictor of postvaccination antibody levels, irrespective of age.

The Advisory Committee on Immunization Practices recommends annual influenza vaccination for all persons aged ≥6 months to reduce morbidity and mortality caused by influenza in the United States. CDC previously developed a model to estimate that annual influenza vaccination resulted in 1.1-6.6 million fewer cases and 7,700-79,000 fewer hospitalizations per season during the 2005-2013 influenza seasons. For the 2013-14 influenza season, using updated estimates of vaccination coverage, vaccine effectiveness, and influenza hospitalizations, CDC estimates that influenza vaccination prevented approximately 7.2 million illnesses, 3.1 million medically attended illnesses, and 90,000 hospitalizations associated with influenza. Similar to prior seasons, fewer than half of persons aged ≥6 months are estimated to have been vaccinated. If influenza vaccination levels had reached the Healthy People 2020 target of 70%, an estimated additional 5.9 million illnesses, 2.3 million medically attended illnesses, and 42,000 hospitalizations associated with influenza might have been averted. For the nation to more fully benefit from influenza vaccines, more effort is needed to reach the Healthy People 2020 target.

Objective: The purpose of this study was to use population-based information to describe the demographic and tumor characteristics of inflammatory breast cancer (IBC)– the most aggressive form of this disease. Methods: IBC cases diagnosed during 1994 through 1998 were reported to 26 population-based cancer registries covering approximately 40% of the US population. Rates were expressed per 100,000 female population and age-adjusted to the 2000 US population. Ninety-five percent gamma confidence limits were estimated for the rates. Results: Among the 3626 women diagnosed with IBC during 1994–1998, the majority were 40–59 years old. Most tumors were diagnosed at a regional (68.9%) or distant (25.3%) stage and were poorly differentiated (49.4%). The rate of IBC was 1.3 per 100,000 for all races combined. Black women had the highest risk (1.6) and Asian and Pacific Islander women the lowest (0.7). Conclusions: IBC is an extremely rare form of breast cancer. More precise diagnostic criteria are needed to distinguish it from less aggressive forms of the disease. Future studies should use a population-based design and collect detailed clinical information, including the presence of erythema, edema or peau d'orange appearance of the skin, and other clinical signs of disease.

Objective: In preparation for jointly publishing official government cancer statistics, the Centers for Disease Control and Prevention (CDC) and the National Cancer Institute (NCI) compared incidence rates from NCI's Surveillance Epidemiology and End Results (SEER) program and CDC's National Program of Cancer Registries (NPCR). Methods: Data for 1999 covering 78% of the US population were obtained from SEER and selected NPCR registries that met high quality data criteria. incidence rates (per 100,000 population) were age-adjusted to the 2000 US standard population, and 95% gamma confidence intervals were estimated Results: NPCR rates for all sites combined were higher than SEER rates (males: NPCR 553.6, SEER 538.7; females: NPCR 420.8, SEER 412.5), but rates for specific cancer sites varied by registry program. Rates for colon cancer (males: NPCR 47.0, SEER 42.7; females: NPCR 36.5, SEER 33.8) and tobacco-related cancers were higher in NPCR than SEER. In contrast, NPCR rates were lower than SEER rates for cancers of the female breaset (NPCR 134.0, SEER 135.9), prostate (NPCR 162.0, SEER 170.2), and melanoma as well as for cancers more common among Asians and Pacific Islanders (e.g., stomach cancer).Conclusions: Rate differences may arise from population difference in socio-demographic characteristics, screening use, health behaviors, exposure to cancer causing agents or registry operations factors.

Purpose There have been speculations that increases in vaccinations have caused recent increases in wheezing lower respiratory disease during infancy. We assess possible associations between vaccines and incidence of wheezing in full-term infants. Methods We conducted a matched case–control study of full-term infants born into the Kaiser Permanente Northwest health plan during 1991–1994 and continuously enrolled for at least 12 months (n = 1366 case–control pairs). Potential cases of wheeze were ascertained from medical care databases and verified by chart review. Vaccinations, demographic factors, and wheeze risk factors were abstracted from charts. Adjusted relative risks of first onset of wheeze during post-vaccination exposure windows were estimated by conditional logistic regression. We also conducted case-series analyses of wheeze onsets. Results We found no evidence that risk of wheeze during infancy is associated with recency of vaccination with whole-cell pertussis (DTP), hepatitis b (HBV), Haemophilus influenzae type b (HIB), oral polio (OPV), or measles, mumps and rubella (MMR) vaccines. We also found no evidence that risk of first wheeze is associated with exposure to HBV or MMR. Conclusions Recent increases in wheezing during infancy do not appear to be related to increases in vaccinations of full-term infants. Published in 2002 by John Wiley & Sons, Ltd.

Background: Young children are at increased risk of severe outcomes from influenza illness, including hospitalization. We conducted a case-control study to identify risk factors for influenza-associated hospitalizations among children in US Emerging Infections Program sites. Methods: Cases were children 6–59 months of age hospitalized for laboratory-confirmed influenza infections during 2005–2008. Age- and zip-code-matched controls were enrolled. Data on child, caregiver and household characteristics were collected from parents and medical records. Conditional logistic regression was used to identify independent risk factors for hospitalization. Results: We enrolled 290 (64%) of 454 eligible cases and 1089 (49%) of 2204 eligible controls. Risk for influenza hospitalization increased with maternal age 50% of household members (OR: 2.9, 95% CI: 1.4–6.6); lack of household influenza vaccination (OR: 1.8, 95% CI: 1.2–2.5) and presence of chronic illnesses, including hematologic/oncologic (OR: 11.8, 95% CI: 4.5–31.0), pulmonary (OR: 2.9, 95% CI: 1.9–4.4) and neurologic (OR: 3.8, 95% CI: 1.6–9.2) conditions. Full influenza immunization decreased the risk among children 6–23 months of age (OR: 0.5, 95% CI: 0.3–0.9) but not among those 24–59 months of age (OR: 1.5, 95% CI: 0.8–3.0; P value for difference = 0.01). Conclusions: Chronic illnesses, young maternal age, poverty, household smoking and lack of household influenza vaccination increased the risk of influenza hospitalization. These characteristics may help providers to identify young children who are at greatest risk for severe outcomes from influenza illness.

Objective: Influenza can exacerbate asthma, particularly in children. The effectiveness of influenza vaccine in preventing influenza-related asthma exacerbations, however, is not known. We evaluated influenza vaccine effectiveness in protecting children against influenza-related asthma exacerbations. Study design: We conducted a population-based retrospective cohort study with medical and vaccination records in 4 large health maintenance organizations in the United States during the 1993-1994, 1994-1995, and 1995-1996 influenza seasons. We studied children with asthma who were 1 through 6 years of age and who were identified by search of computerized databases of medical encounters and pharmacy dispensings. Main outcome measures were exacerbations of asthma evaluated in the emergency department or hospital. Results: Unadjusted rates of asthma exacerbations were higher after influenza vaccination than before vaccination. After adjustment was done for asthma severity by means of a self-control method, however, the incidence rate ratios of asthma exacerbations after vaccination were 0.78 (95% CI: 0.55 to 1.10), 0.59 (0.43 to 0.81), and 0.65 (0.52 to 0.80) compared with the period before vaccination during the 3 influenza seasons. Conclusions: After controlling for asthma severity, we found that influenza vaccination protects against acute asthma exacerbations in children. (J Pediatr 2001;138:306-10)

CONTEXT Although influenza vaccination is recommended for children with asthma, only a minority are vaccinated. One reason for low influenza vaccine coverage among children with asthma may be concern that influenza vaccination may induce an exacerbation of asthma. OBJECTIVE To evaluate the safety of influenza vaccination in children with asthma, we studied the incidence of hospitalizations and emergency department visits for asthma following influenza vaccination. DESIGN Retrospective cohort study-analysis of population-based computerized medical and vaccination records. SETTING : Four large health maintenance organizations on the West Coast of the United States. SUBJECTS Children with asthma 1 through 6 years of age, identified by search of computerized databases of medical encounters and pharmacy prescriptions. MAIN OUTCOME MEASURES Exacerbations of asthma. RESULTS In unadjusted analyses vaccination was associated with high rates of asthma exacerbations. However, after adjusting for asthma severity using a self-control method, the incidence rate ratios of asthma exacerbations after vaccination were 0.58 (95% confidence interval, 0.36-0.95), 0.74 (95% confidence interval, 0.47-1.17), and 0.98 (95% confidence interval, 0.76-1.27) during the 3 influenza seasons. CONCLUSIONS After controlling for asthma severity, we found that influenza vaccination does not result in acute asthma exacerbations in children. Concern about possible exacerbation of asthma is not a valid reason to not vaccinate children with asthma against influenza.

We assessed vaccination coverage and predictors of influenza vaccination in asthmatic children in four large Health Maintenance Organizations. We studied 68,839 children with asthma at four Health Maintenance Organizations (HMOs) in the 1995-1996 influenza season and 34,032 children at two HMOs in the 1996-1997 influenza season. In both seasons only 9-10% were vaccinated against influenza. Children who were hospitalized, had an emergency department visit for asthma or a prescription for a beta-agonist prior to the influenza season, were more likely to be vaccinated. Overall, 61% of the unvaccinated asthmatic children had made an outpatient clinic visit during months when influenza vaccination would have been appropriate. Vaccination coverage could be increased by taking advantage of all opportunities to vaccinate children with asthma whenever they make clinic visits in the fall and early winter.

Several studies suggest that toxic chemicals in hair products may be absorbed through the scalp in sufficient amounts to increase the risks of adverse health effects in women or their infants. This case-control study of 525 Black women from three counties in North Carolina who had delivered a singleton, liveborn infant examined whether exposure to chemicals used in hair straightening and curling increased the odds that the infant was preterm or low birth weight. Cases consisted of 188 preterm and 156 low birth weight births (for 123 women, their infant was both low birth weight and preterm). Controls were 304 women who delivered term and normal birth weight infants. Women who used a chemical hair straightener at any time during pregnancy or within 3 months prior to conception had an adjusted odds ratios (OR) of 0.7 (95% confidence interval (CI) 0.4-1.1) for preterm birth and 0.6 (95% CI 0.4-1.1) for low birth weight. Exposure to chemical curl products was also not associated with preterm delivery (adjusted OR = 0.9, 95% CI 0.5-1.8) or low birth weight (adjusted OR = 1.0, 95% CI 0.5-1.9). Despite this failure to find an association, continued search for risk factors to which Black women are uniquely exposed is warranted.

Corrigendum to “Influenza vaccine effectiveness among 50–64-year-old persons during a season of poor antigenic match between vaccine and circulating influenza virus strains: Colorado, United States, 2003–2004” [Vaccine 25 (1) (2006) 154–160] Guillermo A. Herreraa, Marika K. Iwanea,∗, Margaret Cortesea, Cedric Browna, Ken Gershmanb, Alyson Shupeb, Francisco Averhoffa, Sandra S. Chavesa, Paul Gargiulloa, Carolyn B. Bridgesa

Objectives. Currently, no surveillance system collects data on the numbers and characteristics of vasectomies performed annually in the United States. This study provides nationwide data on the numbers of vasectomies and the use of no-scalpel vasectomy, various occlusion methods, fascial interposition, and protocols for analyzing semen after vasectomy. Methods. A retrospective mail survey (with telephone follow-up) was conducted of 1800 urology, family practice, and general surgery practices drawn from the American Medical Association’s Physician Master File and stratified by specialty and census region. Mail survey and telephone follow-up yielded an 88% response rate. Results. In 1995, approximately 494,000 vasectomies are estimated to have been performed by 15,800 physicians in the United States. Urologists performed 76% of all vasectomies, and nearly all (93%) urology practices performed vasectomies in 1995. Nearly one third (29%) of vasectomies in 1995 were no-scalpel vasectomies, and 37% of physicians performing no-scalpel vasectomies taught themselves the procedure. The most common occlusion method in 1995 (used for 38% of all vasectomies) was concurrent use of ligation and cautery. In 1995, slightly less than half (48%) of all physicians surveyed interposed the fascial sheath over one end of the vas when performing a vasectomy. Protocols for ensuring azoospermia varied: 56% of physicians required one postvasectomy semen specimen; 39% required two, and 5%, three or more. Conclusions. No-scalpel vasectomy, used by nearly one third of U.S. physicians, has become an accepted part of urologic care. Physicians’ variations in occlusion methods, use of fascial interposition, and postvasectomy protocols underscore the need for large scale, controlled, and statistically valid studies to determine the efficacy of occlusion methods and fascial interposition, as well as whether azoospermia is the only determination of a successful vasectomy.

OBJECTIVE: Our goal was to determine whether vaginal douching was associated with ectopic pregnancy among black women and whether specific douching behaviors were associated with differences in risk. STUDY DESIGN: We analyzed data from a case-control study of ectopic pregnancy conducted between October 1988 and August 1990 at a major public hospital in Atlanta, Georgia. Case subjects were 197 black women with surgically confirmed ectopic pregnancies; the control group included 882 black women who were delivered of live or stillborn infants and 237 black women who were seeking to terminate a pregnancy. RESULTS: The adjusted odds ratio for ectopic pregnancy associated with ever having douched was 3.8 (95% confidence interval 1.6 to 8.9). The risk increased with increasing number of years of douching at least once per month. No douching behavior was found to be without risk; even women who douched for routine cleanliness were at increased risk of ectopic pregnancy. CONCLUSIONS: Vaginal douching is a modifiable behavior that may greatly increase a woman's risk of ectopic pregnancy. (Am J Obstet Gynecol 1997;176:991-7.)

Objective. To assess the risk of ectopic pregnancy by the number of previous induced abortions.Design. Prospective cohort study.Methods. Three thousand seven hundred and fifty-four women, 39 years old or younger, living permanently in one Norwegian county, who had had at least one induced abortion between January 1, 1987 and December 31, 1992, at the University Hospital of Trondheim, Norway were followed prospectively for histologically verified ectopic pregnancies until December 31, 1993. Exposure time was measured from the most recent induced abortion (index abortion) until the ectopic pregnancy, closure date, or the subject's 40th birthday. Statistical analyses were done in SAS applying survival analyses and poisson regression.Results. During the follow-up period of 164,167 women-months, we observed 24 ectopic pregnancies in 3,754 women. The adjusted incidence density ratio (alDR) for women who had had two or more induced abortions was 1.2 (95% CI: 0.5-3.1) in comparison with the reference group of wom...

Summary Background The influenza A (H1N1) 2009 monovalent vaccination programme was the largest mass vaccination initiative in recent US history. Commensurate with the size and scope of the vaccination programme, a project to monitor vaccine adverse events was undertaken, the most comprehensive safety surveillance agenda in the USA to date. The adverse event monitoring project identified an increased risk of Guillain-Barre syndrome after vaccination; however, some individual variability in results was noted. Guillain-Barre syndrome is a rare but serious health disorder in which a person's own immune system damages their nerve cells, causing muscle weakness, sometimes paralysis, and infrequently death. We did a meta-analysis of data from the adverse event monitoring project to ascertain whether influenza A (H1N1) 2009 monovalent inactivated vaccines used in the USA increased the risk of Guillain-Barre syndrome. Methods Data were obtained from six adverse event monitoring systems. About 23 million vaccinated people were included in the analysis. The primary analysis entailed calculation of incidence rate ratios and attributable risks of excess cases of Guillain-Barre syndrome per million vaccinations. We used a self-controlled risk-interval design. Findings Influenza A (H1N1) 2009 monovalent inactivated vaccines were associated with a small increased risk of Guillain-Barre syndrome (incidence rate ratio 2·35, 95% CI 1·42–4·01, p=0·0003). This finding translated to about 1·6 excess cases of Guillain-Barre syndrome per million people vaccinated. Interpretation The modest risk of Guillain-Barre syndrome attributed to vaccination is consistent with previous estimates of the disorder after seasonal influenza vaccination. A risk of this small magnitude would be difficult to capture during routine seasonal influenza vaccine programmes, which have extensive, but comparatively less, safety monitoring. In view of the morbidity and mortality caused by 2009 H1N1 influenza and the effectiveness of the vaccine, clinicians, policy makers, and those eligible for vaccination should be assured that the benefits of inactivated pandemic vaccines greatly outweigh the risks. Funding US Federal Government.

Context: The goal of influenza vaccination programs is to reduce influenza-associated disease outcomes. Therefore, estimating the reduced burden of influenza as a result of vaccination over time and by age group would allow for a clear understanding of the value of influenza vaccines in the US, and of areas where improvements could lead to greatest benefits. Objective: To estimate the direct effect of influenza vaccination in the US in terms of averted number of cases, medicallyattended cases, and hospitalizations over six recent influenza seasons. Design: Using existing surveillance data, we present a method for assessing the impact of influenza vaccination where impact is defined as either the number of averted outcomes or as the prevented disease fraction (the number of cases estimated to have been averted relative to the number of cases that would have occurred in the absence of vaccination). Results: We estimated that during our 6-year study period, the number of influenza illnesses averted by vaccination ranged from a low of approximately 1.1 million (95% confidence interval (CI) 0.6–1.7 million) during the 2006–2007 season to a high of 5 million (CI 2.9–8.6 million) during the 2010–2011 season while the number of averted hospitalizations ranged from a low of 7,700 (CI 3,700–14,100) in 2009–2010 to a high of 40,400 (CI 20,800–73,000) in 2010–2011. Prevented fractions varied across age groups and over time. The highest prevented fraction in the study period was observed in 2010–2011, reflecting the post-pandemic expansion of vaccination coverage. Conclusions: Influenza vaccination programs in the US produce a substantial health benefit in terms of averted cases, clinic visits and hospitalizations. Our results underscore the potential for additional disease prevention through increased vaccination coverage, particularly among nonelderly adults, and increased vaccine effectiveness, particularly among the elderly.

Objective To determine if the increase in the percentage of women who received no prenatal care in the United States relative to 1980 (from 1.3% in 1980 to 2.2% in 1989 and 1.7% in 1992) was due to increasing risks of no care in subgroups of women or increasing percentages of births to women at high demographic risk of no care. Methods We analyzed U.S. birth certificates for the period 1980–1992. The annual adjusted odds of no prenatal care relative to 1980 were computed by logistic regression models that included year, maternal characteristics, and interactions of these characteristics with year. We also examined changes in the annual distributions of births by maternal characteristics. Results The risk of no prenatal care in most subgroups increased during the early 1980s, peaked in the late 1980s, and declined thereafter. For example, among black women, the adjusted risk of no care more than doubled from 1980 to 1989. Throughout the 1980s and into the 1990s, the percentage of births to women at high demographic risk of no care increased. This increase in the percentage of births to women at high demographic risk shows no sign of abating. Conclusions During the 1980s, increasing risks in subgroups of women drove the increase in the crude rate of no prenatal care. Despite decreases in the risks of no care in the early 1990s, increasing percentages of births to women with high demographic risk for no care prevented a decrease in the crude rate to the 1980 level.

Background Intussusception is the most common cause of infant bowel obstruction. Because delays in diagnosis can lead to severe outcomes, differentiating milder cases from those with potentially serious outcomes is important. Objective The objective of this study was to identify factors associated with bowel resection among intussusception cases using data from a large nationwide study, which investigated the association between intussusception and Rotashield. Methods We examined characteristics of 376 intussusception cases not associated with Rotashield use. Cases were confirmed by a radiologic procedure, surgery, or autopsy. Clinical characteristics of infants with and without bowel resection were compared. Results During the week before hospitalization, 93% of the 376 infants with intussusception had vomiting, 72% reported bloody stool, 63% had hemoccult positive stool, 51% had diarrhea, 43% reported fever, and 14% had documented fever. Surgery was performed on 209 cases (56%). Of these 209 cases, 33% (67/209) required bowel resection. Documented fever on admission significantly increased the risk of bowel resection (odds ratio, adjusted for race and sex, 2.7; 95% confidence interval, 1.2-6.0). Among infants with intussusception, the presence of a reported symptom for at least 2 days before hospital admission was also an independent predictor of bowel resection (adjusted odds ratio, 2.7; 95% confidence interval, 1.5-4.8). Conclusions Bowel resection appears to be more likely among intussusception patients with documented fever and symptoms for at least 2 days. However, because resection also occurred among those without fever or prolonged symptoms, severe disease must also be considered in absence of these symptoms.

The overall and indirect effects of immunizing school children with influenza A (H1N1) 2009 pandemic virus vaccine prior to and during the peak of virus circulation were evaluated on student and teacher school absenteeism. We used records collected from late 2009 through early 2010 from schools in four Maine counties. Mixed logistic regression models were used to estimate the daily association between school-level immunization coverage and absenteeism by level of influenza activity, after adjusting for the proportion of students receiving reduced-cost lunches, student minority status, absences adjacent to weekends and Thanksgiving, rural school location, and the circulation of other respiratory viruses. Increasing student immunization coverage was associated with reduced absenteeism during periods of high influenza activity. For example, as immunization coverage during the peak week of pandemic virus circulation increased from 38% to 69% (the 10th and 90th percentiles of observed coverage, respectively), relative reductions in daily absenteeism among all students, unimmunized students, and teachers were 8.2% (95% confidence interval [CI]: 6.5, 9.9), 5.7% (95% CI: 4.2, 7.3), and 8.7% (95% CI: 1.3, 16), respectively. Increased vaccination coverage among school-aged Maine children had modest overall and indirect effects on student and teacher absenteeism, despite vaccination occurring just prior and during peak pandemic virus circulation.

The Centers for Disease Control and Prevention Emerging Infections Program implemented active, population-based surveillance for Guillain-Barré syndrome (GBS) following H1N1 vaccines in 10 states/metropolitan areas. We report additional analyses of these data using self-controlled methods, which avoid potential confounding from person-level factors and co-morbidities.Surveillance officers identified GBS cases with symptom onset during October 2009-April 2010 and ascertained receipt of H1N1 vaccines. We calculated self-controlled relative risks by comparing the number of cases with onset during a risk interval 1-42 days after vaccination with cases with onset during fixed (days 43-84) or variable (days 43-end of study period) control intervals. We calculated attributable risks by applying statistically significant relative risks to an independent estimate of GBS incidence.Fifty-nine GBS cases received H1N1 vaccine with or without seasonal vaccine. The relative risk was 2.1 (95%CI 1.2, 3.5) by the variable-window and 3.0 (95%CI 1.4, 6.4) by the fixed-window analyses. The corresponding attributable risks per million doses administered were 1.5 (95%CI 0.3, 3.4) and 2.8 (95%CI 0.6, 7.4).These attributable risks are similar to those of some previous formulations of seasonal influenza vaccine (about one to two cases per million doses administered), suggesting a low risk of GBS following the H1N1 vaccine that is not clearly higher than that of seasonal influenza vaccines.

Because postlicensure surveillance determined that a previous rotavirus vaccine, RotaShield, caused intussusception in 1 of every 10,000 recipients, we assessed the association of the new monovalent rotavirus vaccine (RV1) with intussusception after routine immunization of infants in Mexico and Brazil.We used case-series and case-control methods to assess the association between RV1 and intussusception. Infants with intussusception were identified through active surveillance at 69 hospitals (16 in Mexico and 53 in Brazil), and age-matched infants from the same neighborhood were enrolled as controls. Vaccination dates were verified by a review of vaccination cards or clinic records.We enrolled 615 case patients (285 in Mexico and 330 in Brazil) and 2050 controls. An increased risk of intussusception 1 to 7 days after the first dose of RV1 was identified among infants in Mexico with the use of both the case-series method (incidence ratio, 5.3; 95% confidence interval [CI], 3.0 to 9.3) and the case-control method (odds ratio, 5.8; 95% CI, 2.6 to 13.0). No significant risk was found after the first dose among infants in Brazil, but an increased risk, albeit smaller than that seen after the first dose in Mexico--an increase by a factor of 1.9 to 2.6 - was seen 1 to 7 days after the second dose. A combined annual excess of 96 cases of intussusception in Mexico (approximately 1 per 51,000 infants) and in Brazil (approximately 1 per 68,000 infants) and of 5 deaths due to intussusception was attributable to RV1. However, RV1 prevented approximately 80,000 hospitalizations and 1300 deaths from diarrhea each year in these two countries.RV1 was associated with a short-term risk of intussusception in approximately 1 of every 51,000 to 68,000 vaccinated infants. The absolute number of deaths and hospitalizations averted because of vaccination far exceeded the number of intussusception cases that may have been associated with vaccination. (Funded in part by the GAVI Alliance and the U.S. Department of Health and Human Services.).