Recent health-related quality of life, but not change, predicted mortality and healthcare utilization.

OBJECTIVE: To assess whether change in HRQOL over a seven-year period was associated with subsequent mortality and hospitalization, after adjusting for important covariates, in a cohort of U.S. Veterans. METHODS: We used data from a cohort of Veterans who completed a HRQOL survey in 1998 (Short-Form 36 for Veterans [SF-36V]) and a 2006 follow-up (SF-12V) HRQOL survey and SF12V scores were calculated at both time-points. We used logistic regression analyses to model the relationship between changes in the SF12-V physical component (PCS) and mental health component (MCS) scores and 1-year hospitalization and 1-year and 3.3-year mortality after the 2006 follow-up survey. RESULTS: 13,900 participants provided data for both the initial and follow-up surveys. We found no significant associations between changes in PCS or MCS and one-year hospitalization after adjusting for follow-up HRQOL and other covariates. We found significant but relatively weak associations between changes in MCS and our mortality outcomes. CONCLUSION: Given the follow-up MCS and PCS, change in PCS over the previous 7 years added little information for predicting mortality and hospitalization Although the change in MCS added some information for predicting mortality. Therefore, knowledge of patient's current HRQOL generally provides meaningful information for predicting subsequent mortality and hospitalization.

Comparison of Side Effects of the 2015-2016 High-Dose, Inactivated, Trivalent Influenza Vaccine and Standard Dose, Inactivated, Trivalent Influenza Vaccine in Adults ≥65 Years.

BACKGROUND: High-dose, inactivated, trivalent influenza vaccine (HD) is associated with higher rates of side effects than standard dose (SD) vaccine, which may represent a barrier to use. METHODS: We surveyed subjects ≥65 years who received either HD or SD vaccine at the Minneapolis Veteran Affairs Health Care System clinics on October 27, 28, or 29, 2015. Research assistants conducted a 17-item telephone survey of influenza vaccine recipients to inquire about self-reported health and symptoms experienced the week after vaccination. RESULTS: A total of 547 HD recipients and 541 SD recipients responded to the survey. The 2 groups were similar at baseline with respect to age, gender, and presence of high-risk medical conditions. At least ≥95% of individuals in both HD and SD groups reported that their overall health was the same or better than usual during the week after vaccination. Thirty-seven percent of HD recipients and 22% of SD recipients reported a local or systemic side effect (P < .001), most of which were mild to moderate. Only 7 of 547 (1.3%) HD recipients and 3 of 541 (0.6%) SD recipients reported a severe side effect (P = .34). There was no significant difference in healthcare visits between the groups. CONCLUSIONS: Side effects were more common among subjects ≥65 years who received HD influenza vaccine compared with SD vaccine. These side effects were well tolerated and were not associated with impairment of general health status. These findings should reassure patients and their providers of the safety and tolerability of the HD influenza vaccine.

Effectiveness of A(H1N1)pdm09 influenza vaccine in adults recommended for annual influenza vaccination.

INTRODUCTION: Because of variability in published A(H1N1)pdm09 influenza vaccine effectiveness estimates, we conducted a study in the adults belonging to the risk groups to assess the A(H1N1)pdm09 MF59-adjuvanted influenza vaccine effectiveness. METHODS: VE against influenza and/or pneumonia was assessed in the cohort study (n>25000), and vaccine effectiveness against laboratory-confirmed A(H1N1)pdm09 influenza was assessed in a matched case-control study (16 pairs). Odds ratios (OR) and their 95% confidence intervals (95% CI) were calculated by using multivariate logistic regression; vaccine effectiveness was estimated as (1-odds ratio)*100%. RESULTS: Vaccine effectiveness against laboratory-confirmed A(H1N1)pdm09 influenza and influenza and/or pneumonia was 98% (84-100%) and 33% (2-54%) respectively. The vaccine did not prevent influenza and/or pneumonia in 18-59 years old subjects, and was 49% (16-69%) effective in 60 years and older subjects. CONCLUSIONS: Even though we cannot entirely rule out that selection bias, residual confounding and/or cross-protection has played a role, the present results indicate that the MF59-adjuvanted A(H1N1)pdm09 influenza vaccine has been effective in preventing laboratory-confirmed A(H1N1)pdm09 influenza and influenza and/or pneumonia, the latter notably in 60 years and older subjects.

Innovative approaches for understanding seasonal influenza vaccine declination in healthcare personnel support development of new campaign strategies.

OBJECTIVE: The main objectives of our study were to explore reasons for seasonal influenza vaccine acceptance and declination in employees of a large integrated healthcare system and to identify underlying constructs that influence acceptance versus declination. Secondary objectives were to determine whether vaccine acceptance varied by hospital location and to identify facility-level measures that explained variability. DESIGN: A national health promotion survey of employees was conducted that included items on vaccination in the 2009-2010 influenza season. The survey was administered with two other institutional surveys in a stratified fashion: approximately 40% of participating employees were randomly assigned to complete the health promotion survey. SETTING: National single-payer healthcare system with 152 hospitals. PARTICIPANTS: Employees of the healthcare system in 2010 who responded to the survey. METHODS: Factor analysis was used to identify underlying constructs that influenced vaccine acceptance versus declination. Mean factor scores were examined in relation to demographic characteristics and occupation. Multilevel logistic regression models were used to determine whether vaccine acceptance varied by location and to identify facility-level measures that explained variability. RESULTS: Four factors were identified related to vaccine declination and were labeled as (1) "don't care," (2) "don't want," (3) "don't believe," and (4) "don't know." Significant differences in mean factor scores existed by demographic characteristics and occupation. Vaccine acceptance varied by location, and vaccination rates in the previous year were an important facility-level predictor. CONCLUSIONS: Results should guide interventions that tailor messages on the basis of particular reasons for declination. Occupation-specific and culturally appropriate messaging should be considered. Continued efforts will be taken to better understand how workplace context influences vaccine acceptance.

Identifying barriers to adult pneumococcal vaccination: an NFID task force meeting.

Pneumococcal infection is common in adults, and invasive disease is associated with a high mortality rate. Pneumococcal polysaccharide vaccine can prevent invasive pneumococcal disease and is recommended for people aged ≥ 65 years and for younger adults with high-risk chronic conditions; however, vaccination rates are suboptimal in all of these groups. A multidisciplinary task force meeting examined ways to increase vaccination rates in the target populations. Barriers to vaccination include lack of awareness of the disease or vaccine among vaccination candidates and health care providers, failure to assume responsibility for vaccination, competing priorities, incomplete or inaccessible documentation of previous vaccines, and health care system delivery challenges. Efforts to address these barriers should use appropriate methods. For example, potential vaccine recipients might be motivated by a message from a community leader, whereas health care providers are more apt to offer a vaccine when reminded that it is a recommended best practice. All health care providers need to accept responsibility for vaccination so that this preventive measure becomes a high priority in the care of patients at risk for serious pneumococcal infection.

Agreement between Internet-based self- and proxy-reported health care resource utilization and administrative health care claims.

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.

Cost-effectiveness and socio-economic aspects of childhood influenza vaccination.

Children have high rates of healthcare utilization due to influenza. In addition, children also transmit influenza to others in their households and the community. The costs of influenza in children include the direct medical care costs from increased outpatient visits and hospitalizations, and also indirect costs due to productivity losses especially for their parents and due to transmission of the virus to others. A variety of studies using different methods and assumptions have assessed the cost-effectiveness of influenza vaccination of children, and many find that vaccination is either cost saving or cost effective.

Telephone survey assessment of household patterns of influenza vaccination, Twin Cities seven county metro area, 2008-2009.

Major national surveys do not collect the influenza vaccination status of all household members, thus limiting current understanding of household influenza vaccination patterns. In an early 2009 telephone survey of 800 households in the metropolitan Minneapolis-St Paul area, household respondents reported the age, gender, and 2008-2009 seasonal influenza vaccination status of all household members. After poststratification to adjust for nonresponse, the full household influenza vaccination rate for multiperson households is 35.2%, partial household influenza vaccination rate is 39.9% and the rate of complete household nonvaccination is 24.9%. Full household influenza vaccination is more common in households with an elderly resident, intermediate in households with a child under 5 years of age, and less common in the remaining households. No household members are vaccinated in approximately 10% of multiperson households with either an elderly adult or young child; the corresponding rate in other households is 32.8%. An estimated 51.4% of households with children over 1 year of age have all children vaccinated against influenza; 43.5% of households with children had no children vaccinated against influenza. Households with younger children are more likely to have all children vaccinated and less likely to have no children vaccinated. We believe this is the first study to describe the prevalence of household influenza vaccination patterns. Continued efforts to monitor and increase household vaccination may be a valuable strategy to protect individuals and communities from influenza.

Attending work while sick: implication of flexible sick leave policies.

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.

Employees' willingness to pay to prevent influenza.

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.

Effect of influenza-like illness and other wintertime respiratory illnesses on worker productivity: The child and household influenza-illness and employee function (CHIEF) study.

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.

Workshop on immunizations in older adults: identifying future research agendas.

Goals for immunization in older adults may differ from those in young adults and children, in whom complete prevention of disease is the objective. Often, reduced hospitalization and death but also averting exacerbation of underlying chronic illness, functional decline, and frailty are important goals in the older age group. Because of the effect of age on dendritic cell function, T cell-mediated immune suppression, reduced proliferative capacity of T cells, and other immune responses, the efficacy of vaccines often wanes with advanced age. This article summarizes the discussion and proceedings of a workshop organized by the Association of Specialty Professors, the Infectious Diseases Society of America, the American Geriatrics Society, the National Institute on Aging, and the National Institute of Allergy and Infectious Diseases. Leading researchers and clinicians in the fields of immunology, epidemiology, infectious diseases, geriatrics, and gerontology reviewed the current status of vaccines in older adults, identified knowledge gaps, and suggest priority areas for future research. The goal of the workshop was to identify what is known about immunizations (efficacy, effect, and current schedule) in older adults and to recommend priorities for future research. Investigation in the areas identified has the potential to enhance understanding of the immune process in aging individuals, inform vaccine development, and lead to more-effective strategies to reduce the risk of vaccine-preventable illness in older adults.

Modeling seasonal influenza outbreak in a closed college campus: impact of pre-season vaccination, in-season vaccination and holidays/breaks.

BACKGROUND: College and university students experience substantial morbidity from influenza and influenza-like illness, and they can benefit substantially from vaccination. Public health authorities encourage vaccination not only before the influenza season but also into and even throughout the influenza season. We conducted the present study to assess the impact of various vaccination strategies including delayed (i.e., in-season) vaccination on influenza outbreaks on a college campus. METHODS/FINDINGS: We used a Susceptible --> Infected --> Recovered (SIR) framework for our mathematical models to simulate influenza epidemics in a closed, college campus. We included both students and faculty/staff in the model and derived values for the model parameters from the published literature. The values for key model parameters were varied to assess the impact on the outbreak of various pre-season and delayed vaccination rates; one-way sensitivity analyses were conducted to test the sensitivity of the model outputs to changes in selected parameter values. In the base case, with a pre-season vaccination rate of 20%, no delayed vaccination, and 1 student index case, the total attack rate (total percent infected, TAR) was 45%. With higher pre-season vaccination rates TARs were lower. Even if vaccinations were given 30 days after outbreak onset, TARs were still lower than the TAR of 69% in the absence of vaccination. Varying the proportions of vaccinations given pre-season versus delayed until after the onset of the outbreak gave intermediate TAR values. Base case outputs were sensitive to changes in infectious contact rates and infectious periods and a holiday/break schedule. CONCLUSION: Delayed vaccination and holidays/breaks can be important adjunctive measures to complement traditional pre-season influenza vaccination for controlling and preventing influenza in a closed college campus.

Sensitivity analyses to estimate the potential impact of unmeasured confounding in causal research.

BACKGROUND: The impact of unmeasured confounders on causal associations can be studied by means of sensitivity analyses. Although several sensitivity analyses are available, these are used infrequently. This article is intended as a tutorial on sensitivity analyses, in which we discuss three methods to conduct sensitivity analysis. METHODS: Each method is based on assumed associations between confounder and exposure, confounder and outcome and the prevalence of the confounder in the population at large. In the first method an unmeasured confounder is simulated and subsequently adjusted. The other two methods are analytical methods, in which either the (adjusted) effect estimate is multiplied with a factor based on assumed confounder characteristics, or the (adjusted) risks for the outcome among exposed and unexposed subjects are adjusted by such a factor. These methods are illustrated with a clinical example on influenza vaccine effectiveness. RESULTS: When applied to a dataset constructed to assess the effect of influenza vaccination on mortality, the three reviewed methods provided similar results. After adjustment for observed confounders, influenza vaccination reduced mortality by 42% [odds ratio (OR) 0.58, 95% confidence interval (CI) 0.46-0.73]. To arrive at a 95% CI including one requires a very common confounder (40% prevalence) with strong associations with both vaccination status and mortality, respectively OR < or =0.3 and OR > or =3.0 (OR 0.79, 95% CI 0.62-1.00). CONCLUSIONS: In every non-randomized study on causal associations the robustness of the results with respect to unmeasured confounding can, and should, be assessed using sensitivity analyses.

Benefits and risks of live attenuated influenza vaccine in young children.

OBJECTIVE: To examine the benefit-risk profile of live attenuated influenza vaccine (LAIV) across a range of clinical scenarios in which we varied assumptions regarding both the percentage of children who would receive LAIV in lieu of trivalent inactivated influenza virus (TIV) and the extent of off-label use. STUDY DESIGN: Model of expected benefits and risks of immunization of young children against influenza. METHODS: We estimated expected numbers of cases of influenza illness (FLU), medically significant wheezing (MSW), and hospitalization in a single influenza season under alternative assumptions regarding use of LAIV in lieu of TIV, based on projections from a large phase III trial. RESULTS: Assuming no use of LAIV in nonindicated children (aged <24 months and those with history of recurrent wheezing or asthma), and 50% use in lieu of TIV among children in the indicated population, there would be 2099 fewer FLU cases per 100,000 children aged 12 to 59 months, and no change in MSW or hospitalization. If LAIV also were used in lieu of TIV among 20% of children aged 12 to 23 months and 20% of children aged 24 to 59 months with a history of recurrent wheezing or asthma, there would be a further reduction of 397 FLU cases and 12 hospitalizations per 100,000 children aged 12 to 59 months, but 51 additional MSW cases. CONCLUSIONS: Our study suggests that even if LAIV were sometimes used inadvertently in clinical practice in young children for whom it is not indicated, the overall balance of expected benefits and risks would remain favorable.

Higher pneumococcal disease vaccination rates needed to protect more at-risk US adults.

Pneumococcal disease, which includes pneumococcal pneumonia, meningitis, and bacteremia, is associated with substantial morbidity, mortality, and health care costs in adults. Advanced age, chronic lung or cardiovascular disease, immunosuppressive conditions, and smoking increase the risk for infection. Despite the availability of an effective pneumococcal polysaccharide vaccine (PPSV23), vaccination rates among adults remain suboptimal. This is of immediate concern given the current H1N1 pandemic, since secondary bacterial infection with Streptococcus pneumoniae is common and can contribute to morbidity and mortality. The Centers for Disease Control and Prevention has recently called for increased efforts to vaccinate recommended persons against pneumococcal disease. Long-term trends including the growth of the elderly population and an increase in the number of patients with chronic conditions also underscore the importance of improving pneumococcal vaccination rates. It is important for health care providers, public health officials, and policy makers to recognize the serious health impact of pneumococcal disease in adults and to ensure increased coverage; at present, this is the best way to protect against invasive pneumococcal infection and its consequences.

Challenges in evaluating influenza vaccine effectiveness and the mortality benefits controversy.

Randomized, controlled trials are the gold standard study design. However, ethical constraints and practical considerations may necessitate other types of studies for evaluating influenza vaccine effectiveness in the elderly--a high priority group for annual vaccination in many countries. Observational studies therefore comprise the bulk of the vaccine effectiveness evidence in older persons, but these types of studies can be susceptible to selection bias and residual confounding. All observational studies should utilize strategies to minimize the impact of bias and confounding. Recent studies questioning the plausibility of reported mortality benefits among vaccinated elderly persons may themselves be based on assumptions that are susceptible to important limitations and multiple biases. Future studies that incorporate prospectively collected information on functional status, life expectancy, and other types of data may provide additional insights into these concerns. At present, even after taking into account the potential for residual bias and confounding, most studies confirm the benefits of vaccination among the elderly for reducing hospitalization and death.

Influenza control in the 21st century: Optimizing protection of older adults.

Older adults (> or =65 years of age) are particularly vulnerable to influenza illness. This is due to a waning immune system that reduces their ability to respond to infection, which leads to more severe cases of disease. The majority ( approximately 90%) of influenza-related deaths occur in older adults and, in addition, catastrophic disability resulting from influenza-related hospitalization represents a significant burden in this vulnerable population. Current influenza vaccines provide benefits for older adults against influenza; however, vaccine effectiveness is lower than in younger adults. In addition, antigenic drift is also a concern, as it can impact on vaccine effectiveness due to a mismatch between the vaccine virus strain and the circulating virus strain. As such, vaccines that offer higher and broader protection against both homologous and heterologous virus strains are desirable. Approaches currently available in some countries to meet this medical need in older adults may include the use of adjuvanted vaccines. Future strategies under evaluation include the use of high-dose vaccines; novel or enhanced adjuvantation of current vaccines; use of live attenuated vaccines in combination with current vaccines; DNA vaccines; recombinant vaccines; as well as the use of different modes of delivery and alternative antigens. However, to truly evaluate the benefits that these solutions offer, further efficacy and effectiveness studies, and better correlates of protection, including a precise measurement of the T cell responses that are markers for protection, are needed. While it is clear that vaccines with greater immunogenicity are required for older adults, and that adjuvanted vaccines may offer a short-term solution, further research is required to exploit the many other new technologies.

Human coronavirus and acute respiratory illness in older adults with chronic obstructive pulmonary disease.

BACKGROUND: The clinical features and incidence of human coronavirus (HCoV) infections in chronically ill older adults need better definition. METHODS: HCoV infection was determined on the basis of a 4-fold increase in serum antibody and the detection of HCoV by reverse-transcription polymerase chain reaction. Laboratory-documented influenza (LDI) was detected by serologic assay and culture. HCoV illnesses were compared with other acute respiratory illnesses identified by active surveillance, during the 1998-99 winter respiratory-virus season, of 2215 patients with chronic obstructive pulmonary disease who were > or = 50 years old and who received influenza vaccines. RESULTS: HCoV-229E and HCoV-OC43 were associated with 90 (14%) of 665 illnesses (HCoV-229E in 22, HCoV-OC43 in 67, and both in 1), LDI with 107 (16%) of 678 illnesses. In multivariate logistic regression analysis, myalgia was less likely with HCoV infection than with LDI (OR, 0.27 [95% confidence limit, 0.13-0.58]). A majority of these HCoV and LDI illnesses exhibited each of 11 symptoms and signs of acute respiratory illness. Spirometric results worsened most often with LDI, and many acute respiratory illnesses, regardless of etiology, were associated with hospitalization. A total of 8 illnesses were associated with HCoV-NL63, 1 with HCoV-HKU1. CONCLUSIONS: The frequencies of HCoV and LDI illnesses were similar. HCoV illness was less severe than LDI illness, was accompanied by multiple respiratory and systemic symptoms, and was associated with hospitalization.