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Participants in studies investigating COVID-19 vaccines commonly report reactogenicity events, and concerns about side effects may lead to a reluctance to receive updated COVID-19 vaccinations. A real-world, post hoc analysis, observational 2019nCoV-406 study was conducted to examine reactogenicity within the first 2 days after vaccination with either a protein-based vaccine (NVX-CoV2373) or an mRNA vaccine (BNT162b2 or mRNA-1273) in individuals who previously completed a primary series. Propensity score adjustments were conducted to address potential confounding. The analysis included 1130 participants who received a booster dose of NVX-CoV2373 ( n = 303) or an mRNA vaccine ( n = 827) during the study period. Within the first 2 days after vaccination, solicited systemic reactogenicity events (adjusted) were reported in 60.5% of participants who received NVX-CoV2373 compared with 84.3% of participants who received an mRNA vaccine; moreover, 33.9% and 61.4%, respectively, reported ≥3 systemic reactogenicity symptoms. The adjusted mean (95% CI) number of systemic symptoms was 1.8 (1.6-2.0) and 3.2 (3.0-3.4), respectively. Local reactogenicity events (adjusted) were reported in 73.4% and 91.7% of participants who received NVX-CoV2373 and mRNA vaccines, respectively; the adjusted mean (95% CI) number of local symptoms was 1.5 (1.33-1.61) and 2.4 (2.31-2.52), respectively. These results support the use of adjuvanted, protein-based NVX-CoV2373 as an immunization option with lower reactogenicity than mRNAs.

As SARS-CoV-2 variants continue to emerge, vaccination remains a critical tool to reduce the COVID-19 burden. Vaccine reactogenicity and the impact on work productivity/daily activities are recognized as contributing factors to vaccine hesitancy. To encourage continued COVID-19 vaccination, a more complete understanding of the differences in reactogenicity and impairment due to vaccine-related side effects across currently available vaccines is necessary. The 2019nCoV-406 study (n = 1367) was a prospective observational study of reactogenicity and associated impairments in adults in the United States and Canada who received an approved/authorized COVID-19 vaccine. Compared with recipients of mRNA COVID-19 booster vaccines, a smaller percentage of NVX-CoV2373 booster recipients reported local and systemic reactogenicity. This study's primary endpoint (percentage of participants with ≥50% overall work impairment on ≥1 of the 6 days post-vaccination period) did not show significant differences. However, the data suggest that NVX-CoV2373 booster recipients trended toward being less impaired overall than recipients of an mRNA booster; further research is needed to confirm this observed trend. The results of this real-world study suggest that NVX-CoV2373 may be a beneficial vaccine option with limited impact on non-work activities, in part due to the few reactogenicity events after vaccination.

Policymakers in the United States (US) recommend coronavirus disease 2019 (COVID-19) vaccination with a monovalent 2023-2024 vaccine formulation based on the Omicron XBB.1.5 variant. We estimated the potential US population-level health and economic impacts of increased COVID-19 vaccine coverage that might be expected with the availability of a protein-based vaccine with simpler storage requirements in addition to messenger ribonucleic acid (mRNA) vaccines. A Markov model was developed to estimate 1-year COVID-19-related costs, cases, hospitalizations, and deaths with and without the availability of a protein-based vaccine option. The model population was stratified by age and risk status. Model inputs were sourced from published literature or derived from publicly available data. Our model estimated that a five-percentage-point increase in coverage due to the availability of a protein-based vaccine option would prevent over 500,000 cases, 66,000 hospitalizations, and 3000 COVID-19-related deaths. These clinical outcomes translated to 42,000 quality-adjusted life years (QALYs) gained and an incremental cost-effectiveness ratio of USD 16,141/QALY from a third-party payer perspective. In sensitivity analyses, outcomes were most sensitive to COVID-19 incidence and severity across age groups. The availability of a protein-based vaccine option in the US could reduce hospitalizations and deaths and is predicted to be cost-effective.

Background: NVX-CoV2373 (Nuvaxovid™ or the Novavax COVID-19 Vaccine, Adjuvanted), the first protein-based COVID-19 vaccine, received emergency use authorization (EUA) as a primary series/booster and is available globally. NVX-CoV2373 primary series demonstrated efficacy rates of 89.7-90.4 % and an acceptable safety profile. This article summarizes safety in adult recipients (aged ≥ 18 years) of primary series NVX-CoV2373 in four randomized placebo-controlled trials., Methods: All participants who received NVX-CoV2373 primary series or placebo (pre-crossover) were included according to actual received treatment. The safety period was from Day 0 (first vaccination) to unblinding/receipt of EUA-approved/crossover vaccine, end of each study (EOS), or last visit date/cutoff date minus 14 days. The analysis reviewed local and systemic solicited adverse events (AEs) within 7 days after NVX-CoV2373 or placebo; unsolicited AEs from after Dose 1 to 28 days after Dose 2; serious AEs (SAEs), deaths, AEs of special interest, and vaccine-related medically attended AEs from Day 0 through end of follow-up (incidence rate per 100 person-years)., Findings: Pooled data from 49,950 participants (NVX-CoV2373, n = 30,058; placebo, n = 19,892) were included. Solicited reactions after any dose were more frequent in NVX-CoV2373 recipients (local, 76 %/systemic, 70 %) than placebo recipients (local, 29 %/systemic, 47 %), and were mostly of mild-to-moderate severity. Grade 3+ reactions were infrequent, with greater frequency in NVX-CoV2373 recipients (local, 6.28 %/systemic, 11.36 %) than placebo recipients (local, 0.48 %/systemic, 3.58 %). SAEs and deaths occurred with similarly low frequency in NVX-CoV2373 (SAEs: 0.91 %, deaths: 0.07 %) and placebo recipients (SAEs: 1.0 %, deaths: 0.06 %)., Interpretation: To date, NVX-CoV2373 has displayed an acceptable safety profile in healthy adults., Funding: Supported by Novavax, Inc., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors are employees and shareholders of Novavax, Inc., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Suboptimal adherence to maintenance medication has been associated with poor outcomes in asthma. This study examined single-inhaler inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) adherence and asthma-related outcomes., Methods: This retrospective observational study of patients with asthma initiating ICS/LABA used data from IQVIA PharMetrics Plus (1 January 2014-31 March 2019). Patients included were ⩾18 years old and had ⩾12 months continuous eligibility before, and ⩾180 days follow-up after, the index date. Adherence was measured as proportion of days covered ([PDC] adherent ⩾ 0.8; non-adherent <0.8) each quarter, with outcomes measured each subsequent quarter. Endpoints were asthma-related overall and severe (inpatient/emergency department [ED] visit) exacerbations, rescue medication use, and asthma-related healthcare resource utilization and costs. Regression models evaluated associations between adherence and outcomes, controlling for repeated measures and differences in baseline characteristics., Results: Overall, 50,037 patients were included (mean age 45.3 years; mean follow-up 23.3 months). Adherent patients were less likely to experience asthma-related overall (adjusted odds ratio [aOR] 95% confidence interval [CI]: 0.942 [0.890, 0.998]; p  = 0.041), or severe exacerbations (aOR [95% CI]: 0.778 [0.691, 0.877]; p  < 0.001) per quarter versus non-adherent patients. Adherent patients had lower severe exacerbation rates (adjusted rate ratio [aRR] [95% CI]: 0.792 [0.702, 0.893]; p  < 0.001) but similar overall exacerbation rates (aRR [95% CI]: 0.993 [0.945, 1.044]; p  = 0.783) versus non-adherent patients. The odds of rescue medication use were lower per 20% PDC increase (aOR [95% CI] short-acting β2 agonist: 0.991 [0.985, 0.996]; p  = 0.001; oral corticosteroid: 0.988 [0.982, 0.995]; p  < 0.001). Adherent patients were less likely to visit EDs per quarter (aOR [95% CI]: 0.775 [0.680, 0.883]; p  < 0.001) and odds of hospitalization were lower per 20% PDC increase (aOR [95% CI]: 0.930 [0.881, 0.982]; p  = 0.009). Across most measures, adherent patients incurred lower costs., Conclusion: This real-world study highlights the short-term clinical and economic benefits of ICS/LABA adherence in asthma, particularly in reducing severe exacerbations.

A health care ecosystem is evolving in which all stakeholders will need to work together, apply new technologies, and use disparate data sources to gain insights, increase efficiencies, and improve patient outcomes. The pharmaceutical industry is leveraging its experience and analytics capabilities to play an important role in this evolution.

Background: Influenza B strains from two distinct lineages (Yamagata and Victoria) have cocirculated over recent years. Current seasonal vaccines contain a single B lineage resulting in frequent mismatches between the vaccine strain and the circulating strain. An Ann Arbor strain quadrivalent live attenuated influenza vaccine (Q/LAIV) containing B strains from both lineages is being developed to address this issue., Objectives: The goal of this study was to evaluate whether Q/LAIV administered intranasally as a single dose to a single nostril, using a blow-fill-seal (BFS) delivery system had a similar immunogenicity and safety profile compared with the licensed trivalent vaccine delivered using the Accuspray device., Patients/methods: Adults aged 18-49 years were randomized to receive one intranasal dose of Q/LAIV delivered using a BFS device (Q/LAIV-BFS; n=1202) or one of two trivalent live attenuated influenza vaccines (T/LAIV) containing one of the corresponding B strains (total T/LAIV, n=598). Primary endpoints were the post-vaccination strain-specific serum hemagglutination inhibition antibody geometric mean titers for each strain. Secondary immunogenicity endpoints, safety, and acceptability of the BFS device were also assessed., Results: Q/LAIV was immunogenically non-inferior to T/LAIV for all four influenza strains. Secondary immunogenicity outcomes were consistent with the primary endpoint. Solicited symptoms and AEs were comparable in both groups. Subjects considered the BFS device to be acceptable., Conclusions: Immune responses to vaccination with Ann Arbor strain Q/LAIV-BFS were non-inferior to those with T/LAIV. Q/LAIV may confer broader protection against seasonal influenza B by targeting both major influenza B lineages., (© 2012 John Wiley & Sons Ltd.)

Objective: Many US firms offer influenza vaccination clinics to prevent lost productivity due to influenza. Strategies to promote and offer vaccination differ, and the economic value of the strategies is unknown., Methods: Decision analytic modeling and Monte Carlo probabilistic sensitivity analyses estimated the one-season cost-consequences of three types of influenza clinics (trivalent inactivated influenza vaccine only, vaccine choice [trivalent inactivated influenza or intranasal {live attenuated influenza} vaccine], or vaccine choice plus incentive) in firms of 50 and 250 employees, from the employer's perspective., Results: On-site influenza vaccination was generally cost-saving over no vaccination. For the scenario of vaccine effectiveness of 70% and intermediate transmissibility, the incremental costs per employee for a firm of 50 employees were -$6.41 (ie, cost savings) for inactivated vaccine only versus no vaccination, -$1.48 for vaccine choice versus inactivated vaccine, and $1.84 for vaccine choice plus incentive versus vaccine choice. Clinics offering a choice of vaccines were slightly less costly under many scenarios. Generally, incremental costs were lower (1) in larger firms; (2) when influenza was assumed to be more contagious; and (3) when vaccine effectiveness was assumed to be higher., Conclusion: Employer-sponsored influenza vaccination clinics are generally cost-saving.

This study examined the initiation and logistics, funding, perceived barriers and benefits, and disruption of school activities by school-located influenza vaccination (SLIV) programs conducted during the 2008-2009 influenza season. Seventy-two interviews using a structured protocol were conducted with 26 teachers, 16 school administrators, and 30 health care professionals from 34 schools in 8 school districts. SLIV programs used a variety of locations, scheduling and staffing options, and methods for receiving parental consent and screening children. Health care professionals were primarily responsible for implementing SLIV programs, and most administrators and health care professionals considered programs easy to initiate. Health care professionals identified successful programs as requiring adequate planning/coordination, a dedicated program coordinator, and a consistent funding source. Most respondents (96%) reported minimal school-day disruptions. The perception of most stakeholders is that SLIV programs can be relatively easy to initiate, minimally disruptive and can become more efficient with experience, especially with feedback from all stakeholders.

Objectives: Although Internet-based surveys are becoming more common, little is known about agreement between administrative claims data and Internet-based survey self- and proxy-reported health care resource utilization (HCRU) data. This analysis evaluated the level of agreement between self- and proxy-reported HCRU data, as recorded through an Internet-based survey, and administrative claims-based HCRU data., Methods: The Child and Household Influenza-Illness and Employee Function study collected self- and proxy-reported HCRU data monthly between November 2007 and May 2008. Data included the occurrence and number of visits to hospitals, emergency departments, urgent care centers, and outpatient offices for a respondent's and his or her household members' care. Administrative claims data from the MarketScan® Databases were assessed during the same time and evaluated relative to survey-based metrics. Only data for individuals with employer-sponsored health care coverage linkable to claims were included. The Kappa (κ) statistic was used to evaluate visit concordance, and the intraclass correlation coefficient was used to describe frequency consistency., Results: Agreement for presence of a health care visit and the number of visits were similar for self- and proxy-reported HCRU data. There was moderate to substantial agreement related to health care visit occurrence between survey-based and claims-based HCRU data for inpatient, emergency department, and office visits (κ: 0.47-0.77). There was less agreement on health care visit frequencies, with intraclass correlation coefficient values ranging from 0.14 to 0.71., Conclusions: This study's agreement values suggest that Internet-based surveys are an effective method to collect self- and proxy-reported HCRU data. These results should increase confidence in the use of the Internet for evaluating disease burden., (Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: While annual influenza vaccination is recommended by the CDC for children 6 months and older, vaccination rates remain suboptimal. For healthy, US children 2 years of age and older, influenza vaccine is available as an intramuscular injection (TIV) or an intranasal spray (LAIV), respectively. Little is known about children's experiences and preferences for influenza vaccine attributes., Objective: To examine preferences for influenza vaccine attributes and their relative importance among children., Methods: A quantitative web-survey was administered to children aged 8-12 years sampled from a standing online panel representative of the US population. Children were stratified by age, gender and parent's influenza vaccination behavior. The survey included questions to ascertain children's preferences for influenza vaccine attributes, including efficacy, chance of common side effects, and mode of administration. It included conjoint (trade-off) questions in which children traded-off different attributes in their choice between two influenza vaccines with differing features. We also surveyed children's comprehension of and ability to complete the conjoint questions., Results: 544 children completed the survey (response rate 37%). Children most frequently selected efficacy as the most important vaccine attribute followed by mode of administration (45% and 31%, respectively). When asked for their preference to receive influenza vaccine as a "shot" or a "nose spray", the majority (69%) preferred the nose spray. An evaluation of children's ability to complete the conjoint survey demonstrated that 85% of the sample was able to complete the conjoint tasks. Analysis of the conjoint responses demonstrated that mode of administration and efficacy had the greatest impact on preferences, with a relative importance of 40.5% and 30.6%, respectively. In a direct comparison of vaccine profiles representing the efficacy, side effects, and other characteristics of LAIV and TIV, 79% of children preferred the LAIV-like profile., Conclusion: Children in the sample had consistent opinions regarding influenza vaccine attributes and consider vaccine efficacy and mode of administration to be important. Children can be informed participants in influenza prevention and can be included in discussions regarding influenza vaccination., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Introduction: In this qualitative study we explored children's perceptions of influenza, preferences for influenza vaccines, and ability to understand "risk" of vaccine adverse effects and different attributes between injectable and intranasal vaccines., Method: In-person, semi-structured interviews were conducted among 28 U.S. children aged 6 through 12 years., Results: Many children understood the concept of influenza illness and believed vaccination was important. Efficacy, adverse effects, and mode of administration affected their preferences for influenza vaccines. Children 8 years of age and older were able to consider multiple attributes when selecting between hypothetical vaccines, and their responses were consistent with their previously stated preferences for individual attributes. Most children would prefer a nasal spray over a shot vaccine when all other vaccine attributes were equal., Discussion: Efficacy, adverse effects, and mode of administration were important factors in children's preferences for influenza vaccine. Children as young as 8 years of age appeared to understand vaccine "risk" and were able to consider multiple attributes simultaneously when choosing between vaccine alternatives., (Copyright © 2011 National Association of Pediatric Nurse Practitioners. Published by Elsevier, Inc. All rights reserved.)

Influenza vaccine is available as an intramuscular injection or an intranasal spray for eligible children. This study was conducted to examine parents' preferences for influenza vaccine attributes and the attributes' relative importance regarding the vaccination of their children. A quantitative Web survey was administered to 500 parents of children aged 2 to 12 years. The survey included general preference questions and conjoint (trade-off) questions. Parents most frequently selected efficacy, risk of temporary side effects, and physician recommendation as important vaccine attributes from a provided list (92%, 75%, and 59%, respectively). For attributes selected as important, parents rated the importance of the attribute; the highest mean importance ratings were given to efficacy, presence of mercury-containing preservative, and physician recommendation.The highest relative importance ratings in the conjoint section were given to efficacy and presence of mercury-containing preservative. Parental education on influenza vaccine efficacy and safety may help to improve pediatric vaccination rates.

This randomized cluster trial was designed to improve workplace influenza vaccination rates using enhanced advertising, choice of vaccine type (intranasal or injectable) and an incentive. Workers aged 18-49 years were surveyed immediately following vaccination to determine factors associated with vaccination behavior and choice. The questionnaire assessed attitudes, beliefs and social support for influenza vaccine, demographics, and historical, current, and intentional vaccination behavior. Of the 2389 vaccinees, 83.3% received injectable vaccine and 16.7% received intranasal vaccine. Factors associated with previous influenza vaccination were older age, female sex, higher education and greater support for injectable vaccine (all P<.02). Current influenza vaccination with intranasal vaccine vs. injectable vaccine was associated with higher education, the study interventions, greater support for the intranasal vaccine and nasal sprays, less support of injectable vaccine, more negative attitudes about influenza vaccine, and a greater likelihood of reporting that the individual would not have been vaccinated had only injectable vaccine been offered (all P<.01). Intentional vaccine choice was most highly associated with previous vaccination behavior (P<.001). A key to long term improvements in workplace vaccination is to encourage first time influenza vaccination through interventions that include incentives, publicity and vaccine choice., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Objective: To examine the impact of various flexible sick leave policies (FSLPs) on workplace attendance of employees with self-reported "severe" influenza-like-illness (ILI) symptoms., Methods: This is a prospective study of employees from three US employers, which involved collection of information on employees' access to FSLPs and monthly experience with ILI and workplace attendance from November 2007 to April 2008. Multivariate analyses were used to estimate the impact of FSLPs on employees' workplace attendance while they were experiencing severe ILI symptoms., Results: Among 793 employees with ILI, the average duration of severe ILI symptoms was 3.0 days. Most employees (71.9%) attended work with severe ILI symptoms, for an average of 1.3 days. Employees who could telework had a 29.7% lower rate of attending work with severe ILI symptoms (P = 0.026)., Conclusions: Employers that implement teleworking policies may be able to reduce employee-to-employee transmission of respiratory illness, including seasonal and pandemic influenza.

Background: Despite the recommendation from the Centers for Disease Control and Prevention that children between the ages of 6 months and 18 years be vaccinated against influenza annually, vaccination rates remain suboptimal., Objectives: This study was conducted to explore factors that influence parents' decisions regarding influenza vaccination for children aged 2 to 12 years, to quantify the relative importance of these factors, to identify an appropriate theoretical model for illustrating the relationships among these factors, and to characterize parents by their likelihood of vaccinating their children against influenza., Methods: A quantitative Web-based survey was administered to a sample of parents from an online panel representative of the US population. Parents were stratified based on self-reported rates of their personal influenza vaccination (every year, sometimes, or never) and the age of their child (2-4 years or 5-12 years). The results were examined by parents' likelihood of vaccinating their child in the next year (high, medium, or low). Participants were asked to rank their agreement with statements representing various beliefs and perceptions about influenza and influenza vaccine on a scale from 1 = strongly agree to 5 = strongly disagree. Parents who indicated that they vaccinate their child every year were asked to select the drivers of their decision to vaccinate; parents who indicated that they never vaccinate their child were asked to select the barriers affecting their decision not to vaccinate; and parents who responded that they sometimes vaccinate their child were asked to select both the drivers and barriers affecting their decision. Participants were then asked to rank the importance of each driver or barrier on a scale from 1 = a little important to 5 = extremely important. Mean agreement ratings were calculated for parents' beliefs and perceptions about influenza and influenza vaccine and were compared across likelihood subgroups. Mean importance ratings of the drivers and barriers to vaccination were also calculated and compared across likelihood subgroups., Results: The survey sample consisted of 500 parents; their mean (SD) age was 37.4 (6.82) years, 57.2% were female, and 78.2% were non-Hispanic white. Among those who reported that they vaccinated their child against influenza every year or sometimes, the major drivers of vaccination were prevention of influenza (95.1%), a doctor's recommendation (89.5%), and the desire to reduce influenza symptoms (83.3%). Among those who reported sometimes or never vaccinating their child against influenza, barriers to vaccination were more variable. The most common barriers were low perceived risk of influenza (46.0%), the perception that the vaccine caused influenza (44.0%), and side effects caused by the vaccine (36.6%). Distinct differences were found in beliefs and perceptions of influenza and influenza vaccine according to respondents' likelihood of vaccination. A high likelihood of vaccination was associated with a greater perceived threat of influenza and less concern about the efficacy and safety of the vaccine. Convenience was an important factor among parents with a medium likelihood of vaccination. The Health Belief Model was identified as an appropriate theoretical framework for illustrating the factors influencing parents' decision-making about influenza vaccination., Conclusions: Prevention of influenza, reduction of influenza symptoms, and doctor recommendation were the main drivers of parents' decision to vaccinate their child against influenza. Barriers to vaccination were more variable and primarily included the risk of adverse effects and the perceived low risk of influenza. Increasing parents' awareness of the threat of influenza and the efficacy and safety of the vaccine, as well as improving the convenience of getting vaccinated, may help improve rates of pediatric influenza vaccination., (2010 Excerpta Medica Inc. All rights reserved.)

Objectives: To quantify employees' preferences, as measured by willingness to pay, to prevent influenza in themselves and in their child and adult household members and to examine factors associated with willingness to pay., Study Design: Prospective observational cohort study of a convenience sample of employees from 3 large US employers. Participants had at least 1 child (< or = 17 years) living in their household for at least 4 days per week., Methods: Each month from November 2007 to April 2008, employees completed Web-based surveys regarding acute respiratory illness in their household. In the final survey, employees were presented with descriptions of influenza and questions regarding their willingness to pay to prevent influenza. Factors associated with willingness to pay were examined using multivariate ordinary least squares regression analysis of the log of willingness to pay., Results: Among 2006 employees, 31.3% were female, the mean age was 41.7 years, 85.3% were of white race/ethnicity, and the mean household size was 4.0. Employees' median (mean) willingness to pay to prevent influenza was $25 ($72) for themselves, $25 ($82) for their adult household members, and $50 ($142) (P <.01) for children. However, influenza vaccination rates were approximately equal for children (27.5%), employees (31.5%), and other adult household members (24.5%). This finding may be explained by barriers such as cost, dislike of vaccinations, and disagreement with national influenza vaccination recommendations, which were significantly associated with lower willingness to pay for prevention of influenza (P <.05)., Conclusion: Employees expressed a stronger preference to prevent influenza in their children than in themselves or other household members; however, modifiable barriers depress vaccination rates.

Acute respiratory illnesses (ARI), comprising influenza-like illness (ILI) and other wintertime respiratory illnesses (ORI), impose substantial health and economic burdens on the United States. Little is known about the impact of ILI among household members (HHM), particularly children, on employees' productivity. To quantify the impact of employee and HHM-ILI and ARI on employee productivity, a prospective, observational cohort study was conducted among employees from three large US companies. Employees who had at least one child living at home (N=2013) completed a monthly survey during the 2007-2008 influenza season, reporting the number of days missed from work and hours of presenteeism due to: (1) personal ILI, (2) HHM-ILI, and (3) personal and HHM-ARI. Employee ILI ranged from 4.8% (April) to 13.5% (February). Employees reporting ILI reported more absences than employees not reporting ILI (72% vs 30%, respectively; P<0.001). Overall, 61.2% of employees surveyed had at least one child with an ILI; these employees missed more days of work due to HHM illness than employees without an ARI-ill child (0.9 days vs 0.3 days, respectively; P<0.001). Employees with ILI were less productive, on average, for 4.8h each day that they worked while sick, 2.5h of which was attributable to ILI. HHM illnesses accounted for 17.7% (1389/7868 days) of employee absenteeism, over half of which was due to HHM-ARI. ILI causes a significant amount of employee absence. Household members, particularly children, comprise a sizable proportion of general illness and injury-related employee absences., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: The Advisory Committee on Immunization Practices (ACIP) recommends influenza vaccinations for all children 6 months to 18 years of age, which includes school-aged children. Influenza immunization programs may benefit schools by reducing absenteeism., Methods: A systematic literature review of PubMed, PsychLit, and Dissertation Abstracts available as of January 7, 2008, was conducted for school-located vaccinations, using search words "School Health Services" and "Immunization Programs"; limited to "Child" (6-12 years) and "Adolescent" (13-18 years) for PubMed and "mass or universal" and (immuniz(*) or immunis(*) or vaccin(*)) and (school or Child or Adolescen(*)) for PsychLit and Dissertation Abstracts. Fifty-nine studies met the criteria for review., Results: Strategies such as incentives, education, the design of the consent form, and follow-up can increase parental consent and number of returned forms. Minimizing out-of-pocket cost, offering both the intramuscular (shot) and intranasal (nasal spray) vaccination, and using reminders can increase vaccination coverage among those whose parents consented. Finally, organization, communication, and planning can minimize the logistical challenges., Conclusions: Schools-based vaccination programs are a promising option for achieving the expanded ACIP recommendation; school-located vaccination programs are feasible and effective. Adhering to lessons from the peer-reviewed scientific literature may help public health officials and schools implement the expanded recommendation to provide the greatest benefit for the lowest cost. Given the potential benefits of the expanded recommendation, both directly to the vaccinated children and indirectly to the community, prospective, well-controlled trials to establish the cost-effectiveness of specific vaccination strategies should be high priorities for future research.

Background: To minimize absenteeism resulting from influenza, employers frequently offer on-site influenza vaccination to employees. Yet the level of uptake of vaccine is low among working adults. This study was designed to increase workplace influenza vaccination rates by offering both a choice of intranasal (LAIV) and injectable (TIV) influenza vaccines to eligible employees, and an incentive for being vaccinated, and by increasing awareness of the vaccine clinic., Design: This study used a stratified randomized cluster trial., Setting/participants: A total of 12,222 employees in 53 U.S. companies with previous influenza vaccine clinics were examined., Interventions: Control sites advertised and offered vaccine clinics as previously done. Choice sites offered LAIV or TIV and maintained their previous advertising level but promoted the choice of vaccines. Choice Plus sites increased advertising and promoted and offered a choice of vaccines and a nominal incentive., Main Outcome Measures: These included vaccination rates among eligible employees. Hierarchic linear modeling (HLM) was used to determine factors associated with vaccination., Results: The overall vaccination rate increased from 39% in 2007-2008 to 46% in 2008-2009 (p<0.001). The difference in vaccination rates for LAIV was 6.5% for Choice versus Control and 9.9% for Choice Plus versus Control (both p<0.001). Rates of TIV increased by 15.9 percentage points in the Choice Plus arm versus Control for workers aged > or =50 years (p=0.024). Rates of TIV did not change in workers aged 18-49 years in either intervention arm or in workers aged > or =50 years in the Choice arm. In HLM analyses, factors significantly associated with increased vaccination were older age, female gender, previous company vaccination rate, and the Choice Plus intervention., Conclusions: An incentive for vaccination, an intensified advertising campaign, and offering a choice of influenza vaccines improved vaccination rates in the workplace., (Copyright (c) 2010 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: This study characterized the degree of change in health-related quality of life (HRQL) associated with change in visual acuity among patients with diabetic retinopathy., Methods: Data are from a randomized, placebo-controlled trial of ruboxistaurin for vision loss in patients with diabetic retinopathy. Visual acuity was quantified as letters on the ETDRS visual acuity chart. HRQL was assessed with the 25-Item Visual Function Questionnaire (VFQ-25) and the SF-36. Patients were categorized into groups based on visual acuity change from baseline to month 18. HRQL change of these groups was compared using general linear models. Regression analyses examined visual acuity change defined continuously., Results: Patients (N = 535) were primarily Caucasian (81.9%) and male (64.1%); mean age = 59.3 years. Compared to patients whose visual acuity did not change, the group with > 10 letters vision loss had significantly greater decreases in all VFQ-25 subscales except ocular pain. SF-36 change scores did not correspond as closely to change in vision. Change in visual acuity defined continuously was significantly associated with change in all VFQ-25 scales except ocular pain (p < 0.0001)., Conclusion: Change in visual acuity was associated with corresponding changes in HRQL among patients with diabetic retinopathy. Previous research has often defined vision loss as a loss of at least 15 letters on the ETDRS visual acuity chart. In the current study, however, a loss of at least 10 letters was associated with substantial declines in HRQL domains such as driving, dependency, role limitations, and mental health. These findings suggest that patients who experience vision loss of at least 10 letters may be appropriate targets of future research and clinical intervention.

Background: The US Advisory Committee on Immunization Practices (ACIP) recently expanded the influenza vaccine recommendation to include children 24-59 months of age. In a large head-to-head randomized controlled trial, live attenuated influenza vaccine, trivalent (LAIV) demonstrated a 54% relative reduction in culture-confirmed influenza illness compared with trivalent inactivated influenza vaccine (TIV) among children aged 24-59 months., Objective: To evaluate the relative cost and benefit between two influenza vaccines (LAIV and TIV) for healthy children 24-59 months of age., Methods: Using patient-level data from the clinical trial supplemented with cost data from published literature, we modeled the cost-effectiveness of these two vaccines. Effectiveness was measured in quality-adjusted life years (QALY) and cases of influenza avoided. The analysis used the societal perspective., Results: Due to its higher acquisition cost, LAIV increased vaccination costs by USD7.72 per child compared with TIV. However, compared with TIV, LAIV reduced the number of influenza illness cases and lowered the subsequent healthcare use of children and productivity losses of parents. The estimated offsets in direct and indirect costs saved USD15.80 and USD37.72 per vaccinated child, respectively. LAIV had a net total cost savings of USD45.80 per child relative to TIV. One-way and probabilistic sensitivity analyses indicated that the model was robust across a wide range of relative vaccine efficacy and cost estimates., Conclusions: Due to its increased relative vaccine efficacy over TIV, LAIV reduced the burden of influenza and lowered both direct health care and societal costs among children 24-59 months of age.

Aims: Different estimates exist regarding the impact of diabetic retinopathy (DR) on health utility. A previously reported prospective observational study has reported much larger decrements in self-reported utility than generic utility data from the UK Prospective Diabetes Study and the Lipids in Diabetes Study. The present study was designed to estimate utility loss using multiple methods., Methods: Detailed health state descriptions reflecting declining DR (five different visual acuity levels), neuropathy and nephropathy were validated with patients and used to elicit utility values from people with DR, people with diabetes and members of the UK general public using standard gamble. In addition, a larger sample of people with retinopathy completed different health-related quality of life measures in an interview [EuroQoL (EQ-5D), Health State Utilities Index (HUI)-3, and National Eye Institute Visual Functioning Questionnaire-25]., Results: The utility scores from the standard gamble interviews were not significantly different between the three groups. There was a decline in utility from 6/6 vision to counting fingers of -0.244. The utility data derived from the generic measures revealed an equivalent decline of -0.41 on both the EQ-5D single index and the HUI-3., Conclusions: This study has re-examined the utility decrements associated with DR and has identified much larger declines in utility than previously reported. The study has also reported the utility values of patients with retinopathy as assessed by standard gamble. We believe that this may be the first study to report utility values for health states associated with vision loss which have been elicited from patients with vision loss.

Background: We estimated the prevalence and the associated burden of illness of symptoms of diabetic peripheral neuropathy (SDPN), diabetic retinopathy (DR), and comorbid SDPN and DR among people with diabetes in the United States aged > or =40 years., Methods: Analyses were conducted on 850 respondents aged > or =40 years with diagnosed diabetes from the combined 1999-2000 and 2001-2002 National Health and Nutrition Examination Surveys. Sampling weights were used to estimate the number of people with diabetes who have SDPN, DR, or comorbid SDPN and DR. Multivariate regression models were used to assess the effects of SDPN, DR, and comorbid SDPN and DR on burden-of-illness measures., Results: Approximately 11.9 million adults in the United States aged > or =40 years have diagnosed diabetes. Of those, 3.9 million (32.7%) have SDPN, 3.3 million (27.4%) have DR, and 1.6 million (13.1%) have comorbid SDPN and DR. Among our sample, those with SDPN [odds ratio (OR)=2.25; 95% confidence interval (95% CI)=1.32-3.83], DR (OR=1.68; 95% CI=1.08-2.61), or comorbid SDPN and DR (OR=2.84; 95% CI=1.26-6.41) were more likely than those without the corresponding condition to have four or more health care visits in the past year. Those of working age (40-65 years) with SDPN (OR=3.23; 95% CI=1.60-6.52), DR (OR=2.94; 95% CI=1.45-5.97), or comorbid SDPN and DR (OR=4.32; 95% CI=2.17-8.63) were more likely unable to work due to physical limitations., Conclusions: SDPN, DR, and comorbid SDPN and DR are prevalent among people with diabetes in the United States aged > or =40 years; each of these complications appears to significantly increase the burden of illness.

Aims: The objective of this study was to describe the proportion and characteristics of patients with type 1 and type 2 diabetes diagnosed with diabetic peripheral neuropathy (DPN) in France, Italy, Spain, and the United Kingdom (UK)., Methods: A cross-sectional survey was administered to general practitioners and diabetes specialists. Existing physicians' records were used to quantify the frequency of DPN diagnoses, and notes from patients' medical charts were used to characterize symptoms., Results: The average number of physicians per country was 41 (range of 34-49). The proportion of diabetes patients diagnosed with DPN ranged from 9.6% (95% CI, 7.1-12.2) in Spain to 23.1% (95% CI, 15.4-30.7) in Italy. Of 913 DPN study patients, 55.0% were male, and 78.5% had type 2 diabetes. Mean age was 64.5+/-12.5 years. A DPN diagnosis was based primarily on symptoms. Approximately 27% of patients had no documented neurological examination. "Prickling" was the most common DPN symptom recorded in France, Italy, and Spain, and "numbness" was the most common in the UK., Conclusions: Country-specific estimates of DPN diagnosis may reflect clinical management of diabetes and DPN. A substantial number of diagnoses were not associated with a record of a neurological examination.

Aim: The objective of this study was to describe the proportion and characteristics of patients diagnosed with diabetic retinopathy (DR) in France, Italy, Spain, and the United Kingdom (UK)., Methods: To estimate the proportion of patients with type 1 and type 2 diabetes diagnosed with DR, we conducted a cross-sectional survey of general practitioners in each country using physician records. In addition, diabetes specialists were recruited in Italy and Spain. We extracted data from the medical notes of a sample of DR patients to characterize DR severity and clinical characteristics., Results: The average number of physicians per country was 41 (range: 34-49). The proportion of diagnosed DR ranged from 10.3% (95% CI, 6.7-14.0%) in Spain to 19.6% (95% CI, 16.0-23.1%) in the UK. Of 752 DR patients studied, 53.9% were male; mean age (+/-SD) was 64.2+/-12.8 years. Consistently across countries, mild non-proliferative DR was the most common severity level of diagnosed DR. Proliferative DR (PDR) ranged from 19.7% (France) to 31.5% (UK). Diabetic macular oedema was reported in approximately 10% of patients. Hypertension (73.1%), dyslipidemia (63.2%), and neuropathy (52.1%) were the most common co-morbidities., Conclusions: Country-specific prevalence of diagnosed DR may reflect clinical management of diabetes, healthcare systems, or record-keeping accuracy. Across countries, up to 30% of DR patients had a diagnosis of PDR, which could suggest that patients are diagnosed only when their disease is advanced.

Background: Limited data are available regarding the cost-effectiveness of preventative therapies for postmenopausal women with osteopenia. The objective of the present study was to evaluate the cost-effectiveness of raloxifene, alendronate and conservative care in this population., Methods: We developed a microsimulation model to assess the incremental cost and effectiveness of raloxifene and alendronate relative to conservative care. We assumed a societal perspective and a lifetime time horizon. We examined clinical scenarios involving postmenopausal women from 55 to 75 years of age with bone mineral density T-scores ranging from -1.0 to -2.4. Modeled health events included vertebral and nonvertebral fractures, invasive breast cancer, and venous thromboembolism (VTE). Raloxifene and alendronate were assumed to reduce the incidence of vertebral but not nonvertebral fractures; raloxifene was assumed to decrease the incidence of breast cancer and increase the incidence of VTEs. Cost-effectiveness is reported in $/QALYs gained., Results: For women 55 to 60 years of age with a T-score of -1.8, raloxifene cost approximately $50,000/QALY gained relative to conservative care. Raloxifene was less cost-effective for women 65 and older. At all ages, alendronate was both more expensive and less effective than raloxifene. In most clinical scenarios, raloxifene conferred a greater benefit (in QALYs) from prevention of invasive breast cancer than from fracture prevention. Results were most sensitive to the population's underlying risk of fracture and breast cancer, assumed efficacy and costs of treatment, and the discount rate., Conclusion: For 55 and 60 year old women with osteopenia, treatment with raloxifene compares favorably to interventions accepted as cost-effective.

Objective: There are limited studies concerning the economic burden of osteoporosis in the Medicaid population. This study estimated the direct cost of osteoporosis-related fractures (OPFx) to state Medicaid budgets., Methods: This retrospective analysis utilized Medicaid claims databases from three states, which included approximately 8 million Medicaid recipients. The study sample had at least one claim for an osteoporosis diagnosis (733.0x) between January 1, 2000 and December 31, 2001. Beneficiaries with a fracture and a diagnosis of osteoporosis were assigned to the case cohort. A propensity score-based matching method was used to select a cohort of controls with osteoporosis but without a fracture. An exponential conditional mean model was used to estimate the incremental annual cost associated with fractures., Results: The study cohort (n = 7626) and a 1:1 matched control group were identified. The study cohort was 85.8% female, had an average age of 65 years, were 53.2% white, and 48.9% were eligible for Medicare. There were significant increases (all P < 0.05) from the preperiod to study period for this cohort in the proportion that had at least one hospital admission (14.0% vs. 26.5%), nursing home admission (9.2% vs. 17.2%), home health (39.1% vs. 49.3%), or emergency room visit (21.3% vs. 31.9%). In contrast, the control cohort had very little increase in utilization. The regression-adjusted incremental cost for osteoporosis-related expenses in the year after fracture was estimated at $4007 per patient. The estimated incremental cost was $5370 for the subset of patients who were eligible for Medicare., Conclusion: The economic burden of osteoporosis-related fractures on state Medicaid budgets is substantial.

Aims: To characterize symptom severity of diabetic peripheral neuropathy (DPN) in people with diabetes and to characterize its association with healthcare resource use., Methods: The study was undertaken in Cardiff and the Vale of Glamorgan, UK. A postal survey was posted to subjects identified as having diabetes. Demography, quality of life (EQ-5D and SF-36) and symptoms of neuropathy (NTSS-6 and QOL-DN) data were collected. These data were linked to routine healthcare data coded into healthcare resource groups (HRGs) and subsequently costed according to UK National reference costs., Results: Survey responses were received from 1298 patients, a 32% response rate. For patients with a clinically confirmed diagnosis of DPN, the mean NTSS-6-SA score was 6.16 vs. 3.19 (P < 0.001). Duration of diabetes did not change across groups defined by severity of neuropathy symptoms, but mean HbA(1c) and body mass index values did increase with symptom severity (range 7.6-8.1%, P = 0.023; and 28.0-30.9 kg/m(2), P < 0.001, respectively). General linear modelling showed that the NTSS-6-SA score was a significant predictor of both annual health resource costs and yearly prescribed drug costs. On average, each 1-point increase in NTSS-6-SA score predicted a 6% increase in primary and secondary care costs and a 3% increase in log transformed drug costs., Conclusion: This study demonstrated that severity of DPN symptoms was associated with increased healthcare resource use, thus costs.

Aims/hypothesis: We characterised symptom severity of diabetic peripheral neuropathy (DPN) in people with diabetes, and correlated this with health-related utility and health-related quality of life., Materials and Methods: The study was undertaken in Cardiff and the Vale of Glamorgan, Wales. A postal survey was mailed to a random sample of subjects identified as having diabetes. Data were collected on the symptoms of neuropathy using the Neuropathic Total Symptom Score (self-administered) (NTSS-6-6A) and on quality of life using the Quality of Life in Diabetes Neuropathy Instrument (QoL-DN), EueroQoL five dimensions (EQ5D) and Short Form 36 (SF36). Other information, such as demographics and self-reported drug use, was also collected. The anonymised data were linked to routine inpatient and outpatient healthcare data., Results: Responses were received from 1,298 patients. For patients with a clinically confirmed diagnosis of DPN, the mean NTSS-6-SA score was 6.16 vs 3.19 in patients without DPN (p<0.001). Four categories of severity were defined, ranging from none to severe. All quality of life measures showed a deterioration between these groups: the EQ5D(index) fell from an average of 0.81 in those without symptoms to 0.25 in those with severe symptoms, the SF36 general health profile fell from 59.9 to 25.5 (p<0.001) and the QoL-DN increased from 25.8 to 48.1 (p<0.001). Multivariate models also demonstrated that this relationship remained after controlling for other factors., Conclusions/interpretation: This study demonstrated that severity of DPN symptoms was predictive of poor health-related utility and decreased quality of life. Furthermore, it provides detailed utility data for economic evaluation of treatment of typical diabetes-related morbidity states. Reducing DPN morbidity should be a priority.

Background: Postmenopausal women have a significant risk of developing a number of chronic conditions including osteoporosis (OP), breast cancer (BrCa), and cardiovascular disease (CVD). These diseases can result in significant direct (medical treatment) and indirect (workplace) costs. The objective of this study is to assess these costs among an employed population., Methods: Deidentified medical and disability claims data from seven large employers (n = 585,441) were analyzed from 1998 through 2000 for female employees, age 50-64 years. Medical claim ICD-9CM codes were used to identify patients treated for: OP (n = 2,314), BrCa (n = 555), and CVD (n = 1,710). Each disease cohort was compared to a random sample of 50- to 64-year-old female employees (n = 7,575). Descriptive and multivariate techniques were used to characterize direct and indirect costs attributable to each condition., Results: Average annual direct costs were higher (p < .001) for female employees treated for OP (6,259 dollars), BrCa (13,925 dollars), or CVD (12,055 dollars) when compared with the random sample (2,951 dollars). In addition, average annual indirect costs associated with OP (4,039 dollars), BrCa (8,236 dollars), and CVD (4,990 dollars) were higher (p < .001) than indirect costs for the random sample (2,292 dollars). Even when controlling for each disease-state cohort's demographics and disease-specific comorbidities, patients treated for OP, BrCa, and CVD continued to have significantly greater direct and indirect costs (p < .001) than the random sample., Conclusions: Chronic conditions such as OP, BrCa, and CVD, which occur more frequently in women after menopause, impose a significant financial burden. Greater health care utilization and work-loss prevalence among women treated for these conditions contribute to these additional costs.

Background: More than 1.5 million fractures occur due to osteoporosis each year. This study examines the annual health care utilization and associated expenditures of osteoporotic patients who sustain a new fragility fracture and of those without a new fracture., Methods and Procedures: The study sample from commercial claims databases consisted of patients enrolled in US plans between January 1, 1997, and December 31, 2001. Patients with both an osteoporosis diagnosis and a related fracture were classified as "osteoporosis with concurrent fracture"; all other osteoporosis patients were classified as "osteoporosis without concurrent fracture." Annual utilization and expenditures for the concurrent-fracture cohort were compared with those without concurrent fracture, as well as with a group of patients without osteoporosis (controls) that was matched to the concurrent-fracture cohort based on age, gender, US region, health plan type, and length of enrollment. Exponential conditional mean models were used to compute regression-adjusted total expenditures across the groups. The differences in adjusted expenditures were used to generate the economic burden-of-illness estimates., Results: Osteoporosis patients with concurrent fracture incurred more than twice the overall health care expenditures in the study period, compared with those without fracture (US $15,942 vs $6,476), and nearly three times those of the control group (US $15,942 vs $4,658). Approximately 25% of the overall health care expenditures (US $4,014 of $15,942) for the concurrent-fracture group were osteoporosis-related expenditures, leading to the conclusion that comorbid conditions in osteoporosis patients with concurrent fracture contribute significantly to overall health care costs. Some of these comorbidity-related costs were likely due to pain-related disorders, which occurred significantly more frequently in the concurrent-fracture cohort than in the other groups., Conclusion: Osteoporosis-related expenditures, particularly those related to fracture, were substantial. However, non-osteoporosis-related expenditures to treat comorbid conditions constituted 75% of the overall health care costs in the year after an osteoporosis-related fracture, which warrants further investigation.

Objective: To provide a descriptive demographic and environmental account of pedestrian injuries among children aged < or =15 years in Jefferson County, Alabama., Methods: This was a retrospective study with a case definition for inclusion of individuals, aged < or =15 years, who suffered a pedestrian injury and sought care at The Children's Hospital of Alabama between 1989 and 1991. Demographic and injury-related information was obtained from the medical record and analyses were performed using t-test and a simple correlation., Results: The majority of the cases were nonwhite, and nearly half had Medicaid or were uninsured. The most common injuries were fractures and closed head trauma. The geographic locations of injury events were not uniformly distributed: a comparison of areas wherein an injury occurred with those that were injury-free revealed a number of significant differences with regard to specific demographic, socioeconomic, and ecological factors., Conclusions: Some of the possible manageable environmental risk factors identified in this study were relatively high posted speed limits; sidewalks that were narrow, absent, or in a state of disrepair; vehicular parking on both sides of the street; and the absence of a divided highway. In this community, the most cost-effective educational intervention may best be targeted to elementary-aged schoolchildren living in areas with low-income families and that have a high density of children.

Background: Previous researchers have reported that newspapers were useful adjuncts to unintentional injury surveillance efforts in a nearby southern state. The current study sought to determine whether newspaper accounts of intentional injuries could provide a reliable source of primary or secondary surveillance data., Methods: Newspaper accounts of assaults, homicides, suicides, and rapes occurring in Jefferson County, Alabama, between January 1, 1991, and December 31, 1991, were compared with similar data from official governmental agencies whose responsibility it is to investigate and/or document the occurrence, details, and characteristics of violent events resulting in death or injury., Results: Newspapers greatly underreported suicides, rapes, and assaults, and reported firearms-related incidents in numbers that substantially exceeded their actual occurrence., Conclusions: Much information of potential value for injury surveillance purposes appears to be excluded from newspapers by editorial process and policy. Thus, newspapers are neither a valid nor reliable source for intentional injury surveillance purposes.

Human surfactant protein A (SPA) expression is considered a marker of respiratory epithelial differentiation. Non-small cell lung cancers (NSCLC) are respiratory epithelial derivatives, and it was previously shown that a minority of these cancers expressed SPA, presumably a consequence of their respiratory epithelial origin. In the studies reported here, SPA-I gene transcriptional regulatory sequences were localized to a 2.75-kb genomic 5'-flanking region fragment obtained by screening a human genomic library. The 2.75-kb fragment was used to direct a luciferase coding sequence transcriptionally within a plasmid construct. In plasmid transduction experiments, the SPA-directed luciferase plasmid produced significant luciferase activity in the SPA-expressing NSCLC cell line, H441, but only background levels in the non-SPA-expressing A549 cells. Because Northern blot analysis of resected NSCLC showed that the majority expressed SPA, an SPA-transcriptional targeting strategy was investigated using chimeric toxin genes comprising the coding sequence for herpes simplex virus thymidine kinase (HSV-TK) under transcriptional control of SPA or SV40 regulatory sequences. As expected, transduction of the constitutive, SV40-directed plasmid followed by ganciclovir treatment reduced numbers of both the A549 and H441 cells. In contrast, the SPA-directed plasmid reduced only the SPA-expressing H441 cells and had no significant effect on the A549 cells. The results of these in vivo experiments suggest the concept of transcriptionally directing toxin genes with SPA can produce targeted toxicity in NSCLC.

Gene therapy may serve as a valuable therapeutic modality for malignancies, such as lung cancer, that are poorly responsive to conventional therapies. Although many methods for transducing new genes into cells have been described, little is known about gene transduction into lung cancer, especially under conditions that might be encountered in clinical use. As a first step in addressing this important issue, the study presented here examined the ability of a recombinant retrovirus to add a selectable marker gene to the A549 non-small cell lung cancer (NSCLC) cell line under a variety of conditions. Examination of viral exposure times ranging from 30 sec to 4 hr revealed that the number of infected cells increased with every increment in time. By increasing the multiplicity of infection to 1.0 and including a polycation, Polybrene, as an infection facilitator, 0.8% of the NSCLC cells were infected with only a 30-sec viral exposure. Nebulization, a potentially attractive route of administration for pulmonary malignancies, had no significant effect on viral titer, proviral structure, or proviral transcripts. A single lyophilization did reduce viral titer by 58 +/- 6%, but did not affect the proviral structure or transcripts produced by the surviving viruses. These results suggest that recombinant retroviruses have the potential to add new genes to malignancies accessible by the airways under conditions likely required for clinical use.