2015-2016 Vaccine Effectiveness of Live Attenuated and Inactivated Influenza Vaccines in Children in the United States.

Background: In the 2015-2016 season, quadrivalent live attenuated influenza vaccine (LAIV) and both trivalent and quadrivalent inactivated influenza vaccine (IIV) were available in the United States. Methods: This study, conducted according to a test-negative case-control design, enrolled children aged 2-17 years presenting to outpatient settings with fever and respiratory symptoms for <5 days at 8 sites across the United States between 30 November 2015 and 15 April 2016. A nasal swab was obtained for reverse-transcriptase polymerase chain reaction (RT-PCR) testing for influenza, and influenza vaccination was verified in the medical record or vaccine registry. Influenza vaccine effectiveness (VE) was estimated using a logistic regression model. Results: Of 1012 children retained for analysis, most children (59%) were unvaccinated, 10% received LAIV, and 31% received IIV. Influenza A (predominantly antigenically similar to the A/California/7/2009 strain) was detected in 14% and influenza B (predominantly a B/Victoria lineage) in 10%. For all influenza, VE was 46% (95% confidence interval [CI], 7%-69%) for LAIV and 65% (48%-76%) for IIV. VE against influenza A(H1N1)pdm09 was 50% (95% CI, -2% to 75%) for LAIV and 71% (51%-82%) for IIV. The odds ratio for vaccine failure with RT-PCR-confirmed A(H1N1)pdm09 was 1.71 (95% CI, 0.78-3.73) in LAIV versus IIV recipients. Conclusions: LAIV and IIV demonstrated effectiveness against any influenza among children aged 2-17 years in 2015-2016. When compared to all unvaccinated children, VE against influenza A(H1N1)pdm09 was significant for IIV but not LAIV. Clinical Trials Registration: NCT01997450.

Recent trends in the prevalence of type 2 diabetes and the association with abdominal obesity lead to growing health disparities in the USA: An analysis of the NHANES surveys from 1999 to 2014.

AIM: To assess whether the secular trends in type 2 diabetes prevalence differ between abdominally obese and non-obese individuals. METHODS: Data from the National Health and Nutrition Examination Surveys (NHANES) were used to estimate the prevalence of type 2 diabetes and abdominal obesity among individuals aged ≥20 years in the USA from 1999/2000 to 2013/2014, after standardization to the age, sex and ethnicity population distribution estimates on January 1, 2014, as published by the US Census Bureau. RESULTS: The prevalence of abdominal obesity in the US population increased from 47.4% (95% confidence interval [CI] 42.6-52.2) in 1999/2000 to 57.2% (95% CI 55.9-58.5) in 2013/2014. A significant increase was observed in all age groups: 20 to 44, 45 to 64, and ≥65 years. The prevalence of type 2 diabetes has also increased from 8.8% (95% CI 7.2-10.4) in 1999/2000 to 11.7% (95% CI 10.9-12.6) in 2013/2014, with no substantial change in trend over the recent years. However, the increase in the prevalence of type 2 diabetes was limited to individuals with abdominal obesity, and more specifically to individuals aged ≥45 years with abdominal obesity, with no significant change in prevalence in the non-obese group and in individuals aged <45 years. CONCLUSION: These findings highlight the critical importance of abdominal obesity-both as a likely key contributor to the continuing epidemic of type 2 diabetes in the USA and as a priority target for public health interventions.

Associations Between Individual Characteristics and Blood Eosinophil Counts in Adults with Asthma or COPD.

BACKGROUND: Elevated blood eosinophil (bEOS) counts are markers of inflammation associated with poorer outcomes in individuals with asthma and chronic obstructive pulmonary disease (COPD). However, little is known about factors impacting the variability of bEOS counts in individuals with these conditions. OBJECTIVE: To determine the association between individual characteristics and bEOS counts in individuals with asthma, COPD, and nonasthma/COPD controls. METHODS: Participants in the National Health and Nutrition Examination Surveys (2001-2016) aged 18 years or older with asthma or COPD and nonasthma/COPD controls were identified on the basis of diagnoses by health care practitioners. Associations between bEOS counts and age, sex, race/ethnicity, body mass index, and smoking status were investigated. Statistical analyses incorporated National Health and Nutrition Examination Surveys multistage sampling and sampling weights. RESULTS: bEOS counts were significantly higher in individuals with asthma than in nonasthma/COPD controls. There was no significant difference between individuals with COPD and nonasthma/COPD controls. Across all 3 populations, median bEOS counts were consistently higher in men (15%-20%) and in those with higher body mass index (∼5%-25%) and lower in individuals of black race (15%-20%). bEOS counts increased with age in nonasthma/COPD controls but not in individuals with asthma or COPD. Among nonasthma/COPD controls and individuals with asthma, bEOS counts were higher in current and former smokers compared with never smokers, but no such association was found between bEOS counts and smoking status in individuals with COPD. CONCLUSIONS: In individuals with asthma or COPD, sex, race, and body mass index should be considered when interpreting bEOS counts. Smoking history should also be considered in individuals with asthma. Future research should evaluate the association between bEOS counts adjusted for demographic factors and clinical outcomes, such as asthma or COPD exacerbations.

Live Attenuated and Inactivated Influenza Vaccine Effectiveness.

BACKGROUND: Researchers in observational studies of vaccine effectiveness (VE) in which they compared quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) among children and adolescents have shown inconsistent results, and the studies have been limited by small samples. METHODS: We combined data from 5 US studies from 2013-2014 through 2015-2016 to compare the VE of LAIV4 and IIV against medically attended, laboratory-confirmed influenza among patients aged 2 to 17 years by influenza season, subtype, age group, and prior vaccination status. The VE of IIV or LAIV4 was calculated as 100% × (1 - odds ratio), comparing the odds of vaccination among patients who were influenza-positive to patients who were influenza-negative from adjusted logistic regression models. Relative effectiveness was defined as the odds of influenza comparingLAIV4 and IIV recipients. RESULTS: Of 17 173 patients aged 2 to 17 years, 4579 received IIV, 1979 received LAIV4, and 10 615 were unvaccinated. Against influenza A/H1N1pdm09, VE was 67% (95% confidence interval [CI]: 62% to 72%) for IIV and 20% (95% CI: -6% to 39%) for LAIV4. Results were similar when stratified by vaccination in the previous season. LAIV4 recipients had significantly higher odds of influenza A/H1N1pdm09 compared with IIV recipients (odds ratio 2.66; 95% CI: 2.06 to 3.44). LAIV4 and IIV had similar effectiveness against influenza A/H3N2 and B. Our overall findings were consistent when stratified by influenza season and age group. CONCLUSIONS: From this pooled individual patient-level data analysis, we found reduced effectiveness of LAIV4 against influenza A/H1N1pdm09 compared with IIV, which is consistent with published results from the individual studies included.

Diabetes and lipid screening among patients in primary care: a cohort study.

BACKGROUND: Obesity is associated with increased cardiovascular diseases and diabetes mellitus. Guidelines call for intensified glucose and lipid screening among overweight and obese patients. Data on compliance with these guidelines are scarce. The purpose of this study was to assess rates of diabetes and lipid screening in primary care according to demographic variables and weight status. METHODS: Over a 3-year follow-up period, we assessed screening rates for blood glucose, triglycerides, and HDL- and LDL-cholesterol among 5025 patients in primary care. From proportional hazards models we estimated screening rates among low, moderate, high, and very-high risk patients and compared them with recommendations of the American Diabetes Association (ADA), National Cholesterol Education Program (ATP III) and U.S. Preventive Services Task Force (USPSTF). RESULTS: Mean (SD) age was 47.4 (15.6); 69% were female, 21% were non-white, and 30% of males and 25% of females were obese (BMI > or = 30 kg/m2). For both diabetes and lipid screening, the adjusted hazard was 260-330% higher among > or = 65 than < 35 year-olds, 50-90% higher in persons with BMI > or = 35 than < 25 kg/m2, 10-30% lower for females than males, and not lower among racial/ethnic minorities. Screening rates were at least 80% among very-high risk persons, which we defined as 55-64 years old, BMI > or = 35 kg/m2, non-white, with baseline hypertension. In contrast, high-risk persons who were younger (35-44 years old) and less obese (BMI 30-<35 kg/m2) were screened less often (43% for LDL-cholesterol among females to 83% for diabetes among males) even though ADA, ATP III and USPSTF recommend diabetes and lipid screening among them. CONCLUSION: Patients with higher BMI or age were more likely to be screened for cardiometabolic risk factors. Women were screened at lower rates than men. Even in a highly structured medical group practice, some obese patients were under-screened for diabetes and dyslipidemia.

Evaluation of the safety of live attenuated influenza vaccine (LAIV) in children and adolescents with asthma and high-risk conditions: a population-based prospective cohort study conducted in England with the Clinical Practice Research Datalink.

OBJECTIVES: To assess the safety of live attenuated influenza vaccine (LAIV) in children in high-risk groups. DESIGN: Non-interventional cohort study. SETTING: England during 2013-2014 and 2014-2015 influenza seasons. PARTICIPANTS: LAIV recipients identified from the Clinical Practice Research Datalink, aged 2-17 years, and with at least one underlying high-risk condition. LAIV recipients were matched with inactivated influenza vaccine (IIV) recipients and unvaccinated controls. PRIMARY OUTCOME MEASURES: Primary safety endpoints were any hospitalisation documented in the linked Hospital Episodes Statistics database within 42 days and up to 6 months after vaccination. RESULTS: 11 463 children and adolescents were included: 4718 received the trivalent LAIV formulation during the 2013-2014 influenza season and 6745 received the quadrivalent formulation during the 2014-2015 influenza season. The risks of hospitalisation within 42 days were 231 per 1000 person-years (95% CI 193 to 275) in season 2013-2014 and 231 (95% CI 198 to 267) in season 2014-2015. These risks were not significantly different when compared with matched unvaccinated children (relative risks (RR) 0.96 (95% CI 0.78 to 1.19) in season 2013-2014, 0.90 (95% CI 0.76 to 1.07) in season 2014-2015) and consistently lower than after IIV administration (RR 0.47 (95% CI: 0.37 to 0.59) in season 2013-2014, 0.42 (95% CI 0.35 to 0.51) in season 2014-2015). A similar pattern was observed up to 6 months postvaccination with a risk of hospitalisation after LAIV administration that did not differ from what was observed in unvaccinated controls and was lower than after IIV administration. CONCLUSIONS: This study did not identify new safety concerns associated with the administration of LAIV in children and adolescents with high-risk conditions. However, as with any other observational study, treatment administration was not randomly assigned and our findings may be confounded by differences between the groups at baseline. TRIAL REGISTRATION NUMBER: EUPAS18527.

Association of Prior Vaccination With Influenza Vaccine Effectiveness in Children Receiving Live Attenuated or Inactivated Vaccine.

Importance: Some studies have reported negative effects of prior-season influenza vaccination. Prior-season influenza vaccination effects on vaccine effectiveness (VE) in children are not well understood. Objective: To assess the association of prior-season influenza vaccination with subsequent VE in children aged 2 to 17 years. Design, Setting, and Participants: This multiseason, test-negative case-control study was conducted in outpatient clinics at 4 US sites among children aged 2 to 17 years with a medically attended febrile acute respiratory illness. Participants were recruited during the 2013-2014, 2014-2015, and 2015-2016 seasons when influenza circulated locally. Cases were children with influenza confirmed by reverse-transcription polymerase chain reaction. Test-negative control individuals were children with negative test results for influenza. Exposures: Vaccination history, including influenza vaccine type received in the enrollment season (live attenuated influenza vaccine [LAIV], inactivated influenza vaccine [IIV], or no vaccine) and season before enrollment (LAIV, IIV, or no vaccine), determined from medical records and immunization registries. Main Outcomes and Measures: LAIV and IIV effectiveness by influenza type and subtype (influenza A[H1N1]pdm09, influenza A[H3N2], or influenza B), estimated as 100 × (1 - odds ratio) in a logistic regression model with adjustment for potential confounders. Prior season vaccination associations were assessed with an interaction term. Results: Of 3369 children (1749 [52%] male; median age, 6.6 years [range, 2-17 years]) included in the analysis, 772 (23%) had a positive test result for influenza and 1674 (50%) were vaccinated in the enrollment season. Among LAIV recipients, VE against influenza A(H3N2) was higher among children vaccinated in both the enrollment and 1 prior season (50.3% [95% CI, 17.0% to 70.2%]) than among those without 1 prior season vaccination (-82.4% [95% CI, -267.5% to 9.5%], interaction P < .001). The effectiveness of LAIV against influenza A(H1N1)pdm09 was not associated with prior season vaccination among those with prior season vaccination (47.5% [95% CI, 11.4% to 68.9%]) and among those without prior season vaccination (7.8% [95% CI, -101.9% to 57.9%]) (interaction P = .37). Prior season vaccination was not associated with effectiveness of IIV against influenza A(H3N2) (38.7% [95% CI, 6.8% to 59.6%] among those with prior-season vaccination and 23.2% [95% CI, -38.3% to 57.4%] among those without prior-season vaccination, interaction P = .16) or with effectiveness of IIV against influenza A[H1N1]pdm09 (72.4% [95% CI, 56.0% to 82.7%] among those with prior season vaccination and 67.5% [95% CI, 32.1% to 84.4%] among those without prior season vaccination, interaction P = .93). Residual protection from prior season vaccination only (no vaccination in the enrollment season) was observed for influenza B (LAIV: 60.0% [95% CI, 36.8% to 74.7%]; IIV: 60.0% [36.9% to 74.6%]). Similar results were observed in analyses that included repeated vaccination in 2 and 3 prior seasons. Conclusions and Relevance: Influenza VE varied by influenza type and subtype and vaccine type, but prior-season vaccination was not associated with reduced VE. These findings support current recommendations for annual influenza vaccination of children.

Live-Attenuated Influenza Vaccine Effectiveness in Children From 2009 to 2015-2016: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis describes and consolidates findings from all studies that assessed the effectiveness of live-attenuated influenza vaccine (LAIV) against laboratory-confirmed influenza since the 2009 pandemic in children and young adults. METHODS: A MEDLINE search was conducted for articles published from January 1, 2010 to November 30, 2016. All original publications reporting an effectiveness estimate of LAIV against cases of influenza confirmed by reverse-transcription polymerase chain reaction or culture were retained for analysis. Effectiveness estimates were categorized by LAIV formulation (monovalent, trivalent, and quadrivalent) and strain (any influenza strain, A(H1N1)pdm09, A(H3N2), and B strains). Consolidated estimates were obtained with a random-effects model. RESULTS: A total of 24 publications presenting 29 observational studies were retained for meta-analysis. Live-attenuated influenza vaccine was not shown to be effective against A(H1N1)pdm09 strains as a monovalent formulation in 2009-2010 or as a trivalent formulation from 2010-2011 to 2013-2014, but consolidated sample sizes were small. It was effective as a quadrivalent formulation but less effective than inactivated influenza vaccine (IIV). Live-attenuated influenza vaccine was consistently effective against B strains and matched A(H3N2) strains but was not shown to provide significant protection against mismatched A(H3N2) strains in 2014-2015. CONCLUSIONS: These findings confirm that effectiveness of LAIV against A(H1N1)pdm09 strains has been lower than IIV. A systematic investigation has been initiated to determine the root cause of the difference in effectiveness between pre- and postpandemic A(H1N1) vaccine strains and to identify a more consistently effective A(H1N1)pdm09 vaccine strain.

Incidence of live-attenuated influenza vaccine administration beyond expiry date in children and adolescents aged 2-17 years in the UK: a population-based cohort study.

OBJECTIVES: To estimate the proportion of live-attenuated influenza vaccine (LAIV) doses administered beyond expiry date in children and adolescents during influenza seasons 2013-2014 and 2014-2015 in the UK. DESIGN: This was a retrospective cohort study. Two cohorts of children and adolescents who received LAIV from 1 September 2013 to 31 March 2014 and from 1 September 2014 to 31 March 2015 and aged 2-17 years at time of LAIV administration were identified from the Clinical Practice Research Datalink (CPRD). SETTING: More than 500 primary care practices in the UK. POPULATION: Proportions of vaccine doses administered beyond expiry date were assessed among 47 396 and 67 099 LAIV recipients with a documented vaccine lot identifier in influenza seasons 2013-2014 and 2014-2015, respectively. INTERVENTION: None. MAIN OUTCOME MEASURE: Administrations of expired LAIV were ascertained by comparison of vaccination dates in CPRD records with expiration dates in AstraZeneca/MedImmune lot distribution data. RESULTS: Overall, 245 LAIV recipients, 80 in 2013-2014 and 165 in 2014-2015, received a dose after its expiration date, yielding proportion estimates of 1.7 per 1000 doses (95% CI 1.3 to 2.1) in season 2013-2014 and 2.5 per 1000 (95% CI 2.1 to 2.8) in season 2014-2015. This proportion increased above 1.0% after December during each season. Most (84% in influenza season 2013-2014 and 59% in influenza season 2014-2015) received an expired dose <30 days after its expiration date. The proportion was higher in London (relative risk 1.93 (95% CI 1.25 to 2.99)) and when the number of LAIV recipients registered in the practice was lower than the median number per practice (relative risk 2.69 (95% CI 1.99 to 3.62)). CONCLUSIONS: Administration of expired LAIV doses occurs infrequently.

Safety of quadrivalent live attenuated influenza vaccine in subjects aged 2-49years.

BACKGROUND: Quadrivalent live attenuated influenza vaccine (Q/LAIV) was licensed in 2012 and replaced trivalent live attenuated influenza vaccine in the United States during the 2013-2014 influenza season. This study assessed the safety of Q/LAIV in children and adults aged 2-49years. METHODS: This was a prospective observational cohort study using data collected from Kaiser Permanente Northern California. Post-vaccination events of interest were any hospitalization, hospitalization for lower respiratory tract infection, and the following medically attended events: hypersensitivity, seizures/convulsions, lower respiratory tract infection, wheezing, Guillain-Barré syndrome, Bell's palsy, encephalitis, neuritis, vasculitis, and narcolepsy/cataplexy. The rates of these events during the risk interval post-vaccination were compared with rates observed during reference periods later in the follow-up (within-cohort analysis) and with rates observed in frequency-matched unvaccinated controls and inactivated influenza vaccine (IIV) recipients. RESULTS: A total of 62,040 eligible Q/LAIV recipients were identified during the 2013-2014 influenza season. Within-cohort comparisons of all Q/LAIV recipients as well as comparisons between Q/LAIV recipients and unvaccinated controls or IIV recipients did not show any significantly higher risk of hospitalizations or medically attended events following administration of Q/LAIV. Additional analyses by setting (clinic visits, emergency department visits, and hospital admissions) and age group (2-4, 5-8, 9-17, and 18-49years) also did not reveal clinically consistent findings that suggested any increased risk after administration of Q/LAIV. CONCLUSION: In this large population study of individuals aged 2-49years, no safety signals associated with the administration of Q/LAIV were observed. A much larger study population would be needed to confidently reject any association between Q/LAIV and very rare events, specifically those with an incidence of <1 event/10,000 person-years. TRIAL REGISTRATION: ClinicalTrials.gov NCT01985997.

Effectiveness of live attenuated influenza vaccine and inactivated influenza vaccine in children during the 2014-2015 season.

BACKGROUND: A clinical study found that live attenuated influenza vaccine (LAIV) was superior to inactivated influenza vaccine (IIV) against drifted A(H3N2) viruses in children. During the 2014-2015 influenza season, widespread circulation of antigenically and genetically drifted A(H3N2) viruses provided an opportunity to evaluate subtype-specific vaccine effectiveness (VE) of quadrivalent LAIV (LAIV4) and IIV in children. METHODS: Children (2-17years) with febrile acute respiratory illness <5days' duration were enrolled at 4 outpatient sites in the United States during the 2014-2015 influenza season. Nasal swabs were tested for influenza by reverse transcription polymerase chain reaction; vaccination dates were obtained from medical records or immunization registries. VE was estimated using a test-negative design comparing odds of vaccination among influenza cases and test-negative controls with adjustment for potential confounders. RESULTS: Among 1696 children enrolled, 1511 (89%) were included in the analysis. Influenza was detected in 427 (28%) children; 317 had influenza A(H3N2) and 110 had influenza B. Most influenza isolates were characterized as a drifted strain of influenza A(H3N2) or a drifted strain of B/Yamagata. For LAIV4, adjusted VE was 50% (95% confidence interval [CI], 27-66%) against any influenza, 30% (95% CI, -6% to 54%) against influenza A(H3N2), and 87% (95% CI, 63-96%) against type B. For IIV, adjusted VE was 39% (95% CI, 18-54%) against any influenza, 40% (95% CI, 16-58%) against A(H3N2), and 29% (95% CI, -15% to 56%) against type B. Odds of influenza for LAIV4 versus IIV recipients were similar against influenza A(H3N2) (odds ratio [OR], 1.17; 95% CI, 0.73-1.86) and lower against influenza B (OR, 0.18; 95% CI, 0.06-0.55). CONCLUSIONS: LAIV4 and IIV provided similar protection against a new antigenic variant A(H3N2). LAIV4 provided significantly greater protection than IIV against a drifted influenza B strain. ClinicalTrials.gov identifier: NCT01997450.

Uptake of childhood influenza vaccine from 2012-2013 to 2014-2015 in the UK and the implications for high-risk children: a retrospective observational cohort study.

OBJECTIVES: To evaluate changes in influenza vaccination rates in healthy and at-risk children following the implementation of the UK's childhood influenza immunisation programme. DESIGN: Observational cohort study before and after initiation of the UK's childhood influenza immunisation programme over three influenza seasons (2012-2013, 2013-2014 and 2014-2015) using data from the Clinical Practice Research Datalink (CPRD). SETTING: More than 500 primary care practices in the UK. POPULATION: All individuals aged 2-17 years on 1 September, with at least 12 months of medical history documented in CPRD were retained in the analysis. INTERVENTION: Starting in 2013-2014, all children aged 2 and 3 years were offered influenza vaccination through general practice, and primary school-aged children were offered influenza vaccination in selected counties in England (described as pilot regions). The vaccination programme was extended to all children aged 4 years in England in 2014-2015. MAIN OUTCOME MEASURE: Cumulative vaccination rate from 1 September to 28 February of the next calendar year as assessed by a time-to-event statistical model (vaccination uptake). Age group, sex, region and type of high-risk medical condition were assessed as predictors. RESULTS: Vaccination uptake increased considerably from 2012-2013 to 2013-2014 in targeted children aged 2-3 years, both in children with a high-risk medical condition (from 40.7% to 61.1%) and those without (from 1.0% to 43.0%). Vaccination rates increased also, though less markedly, in older children. In 2014-2015, vaccination rates remained higher than 40% in healthy children aged 2-3 years, although they decreased slightly from 2013-2014 (from 43.0% to 41.8%). Vaccination rates in older healthy children continued to increase, driven primarily by an increase in children aged 4 years to 31.3% in 2014-2015. CONCLUSIONS: The introduction of a universal childhood vaccination policy in the UK increased vaccination rates for targeted children, including those with high-risk conditions.

A systematic review of the efficacy of live attenuated influenza vaccine upon revaccination of children.

Four randomized, double-blind, placebo-controlled studies in 6090 children that investigated the efficacy of live attenuated influenza vaccine (LAIV) upon revaccination of children against laboratory-confirmed cases of influenza in consecutive seasons were reviewed. The efficacy in season 2 of LAIV administered over 2 consecutive seasons was 86.7% (95 % CI: 76.8%, 92.4%) against strains antigenically similar to those contained in the vaccine. The additional efficacy of LAIV administered in season 2 compared to LAIV recipients in season 1 only was 58.4% (28.3%, 75.9%). LAIV administered over 2 consecutive seasons also was more efficacious than was LAIV administered in season 2 only (relative efficacy: 53.9% [17.4%, 74.3%]). Residual efficacy of LAIV administered in season 1 only compared to placebo administered in two consecutive seasons was 56.4% (37.0%, 69.8%). This review did not find any evidence of decreasing efficacy of LAIV when administered during 2 consecutive seasons.

Association of vaccine handling conditions with effectiveness of live attenuated influenza vaccine against H1N1pdm09 viruses in the United States.

PURPOSE: This analysis examined potential causes of the lack of vaccine effectiveness (VE) of live attenuated influenza vaccine (LAIV) against A/H1N1pdm09 viruses in the United States (US) during the 2013-2014 season. Laboratory studies have demonstrated reduced thermal stability of A/California/07/2009, the A/H1N1pdm09 strain utilized in LAIV from 2009 through 2013-2014. METHODS: Post hoc analyses of a 2013-2014 test-negative case-control (TNCC) effectiveness study investigated associations between vaccine shipping conditions and LAIV lot effectiveness. Investigational sites provided the LAIV lot numbers administered to each LAIV recipient enrolled in the study, and the vaccine distributor used by the site for commercially purchased vaccine. Additionally, a review was conducted of 2009-2014 pediatric observational TNCC effectiveness studies of LAIV, summarizing effectiveness by type/subtype, season, and geographic location. RESULTS: From the 2013 to 2014 TNCC study, the proportion of LAIV recipients who tested positive for H1N1pdm09 was significantly higher among children who received a lot released between August 1 and September 15, 2013, compared with a lot shipped either earlier or later (21% versus 4%; P<0.01). A linear relationship was observed between the proportion of subjects testing positive for H1N1pdm09 and outdoor temperatures during truck unloading at distributors' central locations. The review of LAIV VE studies showed that in the 2010-2011 and 2013-2014 influenza seasons, no significant effectiveness of LAIV against H1N1pdm09 was demonstrated for the trivalent or quadrivalent formulations of LAIV in the US, respectively, in contrast to significant effectiveness against A/H3N2 and B strains during 2010-2014. CONCLUSIONS: This study showed that the lack of VE observed with LAIV in the US against H1N1pdm09 viruses was associated with exposure of some LAIV lots to temperatures above recommended storage conditions during US distribution, and is likely explained by the increased susceptibility of the A/California/7/2009 (H1N1pdm09) LAIV strain to thermal degradation. CLINICAL TRIAL REGISTRY: NCT01997450.

Effectiveness of live attenuated influenza vaccine and inactivated influenza vaccine in children 2-17 years of age in 2013-2014 in the United States.

BACKGROUND: A postmarketing observational study was initiated to evaluate quadrivalent live attenuated influenza vaccine (LAIV) effectiveness in children aged 2-17 years in the United States. METHODS: Children and adolescents aged 2-17 years seeking outpatient care for febrile acute respiratory illness <5 days duration were enrolled at 4 geographically diverse sites during the 2013-2014 influenza season. Nasal swabs were tested for influenza using reverse transcription polymerase chain reaction. Vaccination status was documented from medical records or immunization registries. Children who received ≥1 dose of influenza vaccine ≥14 days before study visit were considered vaccinated. Vaccine effectiveness (VE) was estimated as 100×(1-adjusted odds ratio), where the odds of interest are the odds of vaccine exposure among influenza cases and test-negative controls. RESULTS: In total, 1033 children and adolescents were included in the analysis. Influenza was detected in 14% (145/1033) of all children, with 74% (108/145) of the influenza cases due to A/H1N1pdm09 strains, 21% (31) to influenza B, and 4% (6) to influenza H3N2. LAIV did not show significant effectiveness against A/H1N1pdm09 (VE 13% [95% CI: -55 to 51]) but was effective against B/Yamagata strains (82% [95% CI: 12-96]). Inactivated influenza vaccine was effective against A/H1N1pdm09 (74% [95% CI: 50-86]) and B/Yamagata (70% [95% CI: 18-89]). CONCLUSIONS: LAIV provided significant protection against B/Yamagata influenza but not against A/H1N1pdm09 in children aged 2-17 years in 2013-2014, resulting in a proposed change of the 2015-2016 formulation with a new and more heat-stable A/H1N1pdm09 LAIV strain.

The long-term course of low-density lipoprotein cholesterol after initiation of statin treatment: retrospective database analysis over 3 years in health maintenance organization enrollees.

OBJECTIVES: Our primary objective was to obtain robust estimates of the low-density lipoprotein cholesterol (LDL-C) decrease from baseline over a long period (ie, 3 years) after initiation of statin treatment in a usual-care setting. Our secondary objective was to investigate the predictors of the LDL-C time course. METHODS: We retrospectively analyzed the data for a sample of enrollees in a health maintenance organization (HMO) who started statin treatment between October 1, 1995, and December 31, 1998. Using the HMO's claims database, we examined the LDL-C change from baseline (as measured at the prescribing physicians' discretion) and computed mean estimates every 6 months up to 3 years. We investigated potential predictors of the LDL-C time course (ie, age, sex, baseline LDL-C, previous treatment, prescribing physician's specialty, and most recent treatment) with a mixed model applied to longitudinal data. This model enabled us to impute missing data for all enrollees still being followed, including those who had stopped treatment, and to discuss the robustness of our findings. We applied 2 methods of imputation, assuming either of the following: (1) data were missing at random but could be estimated from the parameters in the mixed model, or (2) LDL-C returned to the baseline value > or =15 days after treatment cessation. RESULTS: We examined data from 3193 individuals. In most cases, the statin used was fluvastatin or pravastatin. The observed mean (95% CI) LDL-C decrease from baseline widened progressively from 23.6% (23.0%-24.3%) at 6 months to 28.0% (27.1%-28.9%) at 18 months and 30.2% (28.7%-31.7%) at 36 months after treatment initiation. These results remained robust after the imputation of missing data, with mean LDL-C reduction consistently >20% at each 6-month time point during the 3 years after treatment initiation. Variations as a function of baseline characteristics were limited (demographics) or explicable by extraneous factors (baseline LDL-C). There were predictable variations as a function of the most recent treatment. CONCLUSIONS: This analysis indicates a long-term reduction in LDL-C among a sample of HMO enrollees who initiated statin treatment in a usual-care setting. The results were robust after imputation of missing data, with mean decrease from baseline consistently >20% over 3 years. However, given the retrospective design of our study and the absence of a control group, we cannot determine how much of the decrease was attributable to treatment.

Compliance with a statin treatment in a usual-care setting: retrospective database analysis over 3 years after treatment initiation in health maintenance organization enrollees with dyslipidemia.

BACKGROUND: Patients treated in a usual-care setting often do not comply with prescribed treatment regimens as closely as those treated in a clinical trial, for a variety of reasons. OBJECTIVES: We sought to describe compliance over 3 years with a statin treatment in an observational study in a usual-care setting and to investigate potential risk factors for poor compliance. METHODS: Enrollees in a Massachusetts health maintenance organization (HMO) who presented with baseline low-density lipoprotein cholesterol (LDL-C) > or =130 mg/dL and who started statin treatment between January 1, 1994, and July 1, 1999, were followed until death, termination of membership in the HMO, or July 1, 1999, whichever came first, as documented by the HMO's drug-dispensing electronic records. The records included information about the demographics, service dates, laboratory data, and filled prescriptions. The outcome measures were time to treatment discontinuation, time to treatment resumption, and adherence to treatment. RESULTS: A total of 4776 enrollees were included in the analysis. Most patients were aged 50 to 69 years (57%), men (52%), had LDL-C > or =160 mg/dL (77%), and received their prescription for antihyperlipidemia therapy from an internist or family physician (87%). The hazard of discontinuation was high during the first 6 months of therapy, with 20% of the initial population discontinuing treatment during this time period, then decreased, so that the fraction of continuing users leveled off: 74%, 65%, and 61% of statin initiators were still on treatment 1, 2, and 3 years after entry, respectively. The probability of resuming statin treatment was 51% within 24 months after last prescription filled. The proportion of adherent users stayed stable, between 53% and 55%, after the first 6 months. Risk factors of treatment discontinuation, treatment resumption, and adherence were remarkably similar and were stable over time. The significant predictors of treatment discontinuation were age <50 years (hazard ratio [HR], 1.45 [95% Cl, 1.26-1.68]), female sex (HR, 1.18 [95% CI, 1.06-1.30], and previous antihyperlipidemia treatment (HR, 0.71 [95% CI, 0.63-0.79]). CONCLUSIONS: In this HMO setting, women and individuals 1026 aged <50 years were at risk for poor compliance with statin therapy. Our analysis suggests that the association between compliance and age or gender may be quite stable over the first 3 years of treatment.

Efficacy of live attenuated influenza vaccine against influenza illness in children as a function of illness severity.

A recent study of inactivated influenza vaccine (IIV) in children aged 3-8 years demonstrated higher efficacy against moderate/severe influenza. A meta-analysis of all previous published randomized clinical trials of live attenuated influenza vaccine (LAIV) that collected information on illness severity in children aged 24-71 months was conducted. Moderate/severe influenza was defined as fever >39°C, acute otitis media, or lower respiratory tract illness; other cases were classified as milder influenza. LAIV efficacy versus placebo was 95.4% [95% confidence interval: 88.5, 98.1] (year 1) and 88.5% [77.4, 94.9] (year 2) against moderate/severe influenza and 91.4% [77.9, 96.7] (year 1) and 84.2% [56.7, 94.3] (year 2) against milder influenza. The relative efficacy of LAIV versus IIV was 52.2% [31.6, 66.6] for moderate/severe influenza and 45.0% [28.6, 57.5] for milder influenza. Efficacy against all influenza illnesses, regardless of severity, is critical to prevent influenza illness and transmission in the community.

Seasonal influenza vaccination trends from 2007-2011 in privately insured children and adults in the United States.

BACKGROUND: To ensure adequate protection from seasonal influenza in the US, the Advisory Committee on Immunization Practices recommends vaccination of all persons aged 6 months or older, with rare exceptions. It also advises starting vaccination as soon as available and continuing throughout the influenza season. This study examined US seasonal vaccination trends during five consecutive influenza seasons in privately-insured children and adults. METHODS: This retrospective, observational cohort study examined trends in influenza vaccination during the 2007-2008 through 2011-2012 influenza seasons using administrative claims data from a large national insurer. RESULTS: The size of analysis population ranged from 1144,098 to 1245,487 (children, ≥6 months-17 years of age) and from 3931,622 to 4158,223 (adults, 18-64 years of age). Vaccination frequency increased through 2010-2011, was most frequent in young children, and decreased with age. Vaccination rates were highest in the Northeast and lowest in the West and were higher in individuals with frequent outpatient office visits than in those with no or rare visits, with larger differences seen in children. Between 2007 and 2011, the use of preservative-free inactivated vaccine increased, the use of multidose vaccines containing preservatives decreased, and the use of live attenuated influenza vaccines increased among children 2-17 years of age. From 2007-2008 through 2009-2010, the timing of vaccination each year began earlier than the previous one; it remained stable from 2009-2010 through 2011-2012. CONCLUSION: Annual influenza vaccination claims for privately-insured children and adults increased and shifted earlier from 2007 through 2009-2011. During the 2011-2012 influenza season, 25.4% of children aged 6 months-17 years and 12.3% of adults aged 18-64 years were vaccinated. Increasing influenza vaccination should remain a priority, and alternative venues for seasonal influenza vaccination should be considered in order to meet the Healthy People 2020 goal of 80% to 90% coverage among children.

Incidence density of serious infection, opportunistic infection, and tuberculosis associated with biologic treatment in patients with rheumatoid arthritis - a systematic evaluation of the literature.

data on the incidence density (ie, incidence per person-year [PY]) of serious infection, opportunistic infection, and tuberculosis associated with each of the nine biologic therapies currently indicated in rheumatoid arthritis patients are not available. To summarize these data, a systematic review was conducted with searches on PubMed and Embase of literature ranging from January 1998 to November 2011. Incidence density was extracted and reported using the definitions from the respective publications. If the incidence density was not reported, estimation was made using available information. A total of 72 published studies met the inclusion criteria and were reviewed, including 44 clinical trials, open-label extension studies, or meta-analyses, and 28 observational studies. Additional calculation of the incidence density was performed in 12 studies for serious infection and in 13 studies for opportunistic infection or tuberculosis. The incidence of serious infection was consistent across studies and biologic therapies, ranging from 0 to 11/100 PY but mainly clustered from 2 to 6/100 PY. Fewer incidence data were available for opportunistic infection and tuberculosis. The incidence of opportunistic infection and tuberculosis ranged widely, from 0.01 to 3.0/100 PY and 0.01 to 2.6/100 PY, respectively. The data on serious infection may be used to evaluate the public health risk and benefit of biologic treatment. They may also serve as a point of reference for future studies. The limited data on opportunistic infection and the lack of a consistent definition of opportunistic infection invite caution for a benchmark rate for opportunistic infection as a composite category.