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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. [ABSTRACT FROM PUBLISHER]

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. [ABSTRACT FROM AUTHOR]

Background. Uncertainties regarding influenza disease impact and benefits of vaccination may contribute to low vaccination rates among adults aged 50-64 years. Methods. This prospective cohort study assessed the burden of influenza-like illness (ILI) among working adults aged 50-64 years and the effectiveness of influenza vaccination in reducing the rate of ILI and productivity losses. Employees of the University of Minnesota (Minneapolis) were invited via e-mail to participate in the study during October 2006. The study data were collected using internet-based surveys at baseline (October 2006) and during the follow-up period (from November 2006 through April 2007). Months included in the 2006-2007 influenza season were identified retrospectively from Minnesota Department of Health surveillance data. Vaccine effectiveness for reducing the rate of ILI, ILI-associated health care use, the number of days of illness, work loss, and reduced on-the-job productivity during the influenza season were assessed using multivariable regression models after controlling for important confounders. Results. Four hundred ninety-seven persons were included in the study, 85 (17.1%) of whom experienced an ILI. Among unvaccinated participants, ILI was responsible for 45% of all days of illness during the influenza season, 39% of all illness-related work days lost, and 49% of all days with illness-related reduced on-the-job productivity. In the multivariable regression analyses, vaccination was associated with a significant reduction in the rate of ILI (adjusted odds ratio, 0.48; 95% confidence interval, 0.27-0.86) and fewer days of illness, absenteeism, and impaired on-the-job performance. Conclusion. ILIs were common among our study participants, accounting for a large portion of illness, work loss, and impaired work performance during the influenza season. Vaccination was associated with substantial health and productivity benefits. Vaccine delivery should be improved for this high-priority group. [ABSTRACT FROM AUTHOR]

Seasonal influenza continues to have a huge annual impact in the United States, accounting for tens of millions of illnesses, hundreds of thousands of excess hospitalizations, and tens of thousands of excess deaths. Vaccination remains the mainstay for the prevention of influenza. In the United States, 2 types of influenza vaccine are currently licensed: trivalent inactivated influenza vaccine and live attenuated influenza vaccine. Both are safe and effective in the populations for which they are approved for use. Children, adults <65 years of age, and the elderly all receive substantial health benefits from vaccination. In addition, vaccination appears to be cost-effective, if not cost saving, across the age spectrum. Despite long-standing recommendations for the routine vaccination of persons in high-priority groups, US vaccination rates remain too low across all age groups. Important issues to be addressed include improving vaccine delivery to current and expanded target groups, ensuring timely availability of adequate vaccine supply, and development of even more effective vaccines. Development of a vaccine against potentially pandemic strains is an essential part of the strategy to control and prevent a pandemic outbreak. The use of existing technologies for influenza vaccine production would be the most straightforward approach, because these technologies are commercially available and licensing would be relatively simple. Approaches currently being tested include subvirion inactivated vaccines and cold-adapted, live attenuated vaccines. Preliminary results have suggested that, for some pandemic antigens, particularly H5, subvirion inactivated vaccines are poorly immunogenic, for reasons that are not clear. Data from evaluation of live pandemic vaccines are pending. Second-generation approaches designed to provide improved immune responses at lower doses have focused on adjuvants such as alum and MF59, which are currently licensed for influenza or other vaccines. Additional experimental approaches are required to achieve the ultimate goal for seasonal and pandemic influenza prevention—namely, the ability to generate broadly cross-reactive and durable protection in humans. [ABSTRACT FROM AUTHOR]

Background. Upper respiratory tract illnesses (URIs) are a major cause of morbidity among adults, with substantial direct and indirect costs to society, but their impact among university students has not been well described. We sought to assess the impact of URIs (colds and influenza-like illnesses [ILIs]) on the health, academic and work performance, and health care use of university students. Methods. This was a cohort study of college students at the University of Minnesota, Twin Cities campus (Minneapolis-St. Paul), who were recruited during October 2002 and followed up from November 2002 through April 2003. All 42,000 registered students were invited via e-mail to participate. Baseline information was obtained in October 2002. Monthly follow-up information about colds or ILIs was obtained for the period of November 2002 through April 2003. Data were collected by use of Internet-based questionnaires. Results. Of 4919 volunteers, 3249 completed all follow-up surveys. The mean age was 22.7 years; 68% of the volunteers were female. Ninety-one percent had ≥1 URI (83% had ≥1 cold, and 36.7% had ≥1 ILI). These URIs caused 6023 bed-days, 4263 missed school days, 3175 missed work days, and 45,219 days of illness. Of the cohort, 22.2% had ≥1 health care visit, and 15.8% used antibiotics to treat a URI; 27.8% did poorly on a test and 46.3% did poorly on a class assignment. ILIs versus colds had a much greater impact on all parameters (e.g., general health level was 55%-60% lower with ILIvs. no URI and 33%-39% lower for colds vs. no URI; P 7lt;.001 for each). Conclusion. Colds and ILIs were common and associated with substantial morbidity in university students. Enhanced efforts to prevent and control URIs, especially influenza vaccination, could improve the health and well- being of the 17 million college and university students in this country. [ABSTRACT FROM AUTHOR]

Background. Three important studies have supported licensure of live, attenuated, cold-adapted influenza vaccine (CAIV-T [FluMist; MedImmune Vaccines]): (1) a pediatric efficacy trial involving children 15–71 months of age, (2) a large safety study of medically attended events occurring among children 1–17 years of age, and (3) an effectiveness trial involving healthy working adults 18–64 years of age. Methods. During the United States Food and Drug Administration (FDA) review for the approval of CAIVT for use in healthy persons, additional subgroup analyses were conducted to evaluate the safety, efficacy, and effectiveness of the vaccine, by use of various age subsets not prespecified by the original protocols. CAIV-T is currently approved by the FDA for use in healthy persons 5–49 years of age. In this article, we present data from some of the aforementioned subanalyses. Results. The efficacy of CAIV-T in children ≥5 years of age (age range of the children in year 1 of the study, 60–71 months; age range of the children in year 2 of the study, 60–83 months) was similar to that reported for the entire cohort in year 1 (90.6%; 95% confidence interval [CI], 70.3%–97.1%). In year 2 of the study, efficacy was 86.9% (95% CI, 70.8%–94.1%), despite the presence of antigenically drifted influenza type A/Sydney/5/97 (H3N2), which caused most illnesses that occurred in year 2. Safety outcomes for children 5–17 years of age revealed no significant difference between vaccine recipients and placebo recipients, with regard to acute respiratory events, acute gastrointestinal events, systemic bacterial infection, or rare events possibly related to influenza. Effectiveness among adults 18–49 years of age was similar to that reported for the entire cohort—for example, for occurrence of severe febrile illness, there was a 19.5% reduction (P=.02) in adults. Conclusions. The present reanalysis summarizes data on the indicated uses for CAIV-T in the indicated population aged 5–49 years. [ABSTRACT FROM AUTHOR]

Uncertainties among health care providers and patients about the risk of serious influenza-associated complications and the potential benefits of vaccination may contribute to unsatisfactorily low influenza vaccination rates. To quantify the risk of serious outcomes (hospitalization due to pneumonia or influenza or death due to any cause) during influenza seasons, we developed a clinical prediction rule for the probability of hospitalization due to pneumonia or influenza or death among elderly persons. Reliability of the regression model was good (P=.65 , by goodness-of-fit test), and it discriminated well between those who did and those who did not experience an outcome (area under the receiver-operating curve, 0.83; 95% confidence interval, 0.81–0.85). Validation revealed moderately lower but acceptable discriminating values (0.72–0.81). In the derivation cohort, the prognostic accuracy of the rule was high when a cutoff score for the upper 50th percentile was used: ≥10 of 1000 subjects with a score in the upper 50th percentile were predicted to have an outcome, and 89% of all outcomes were observed in this high-risk group, whereas <10 of 1000 subjects with a score in the lower 50th percentile were predicted to have an outcome, and only 11% of outcomes occurred in this group. Among unvaccinated subjects in the single-derivation cohort and the 11 validation cohorts combined, the outcome event rates were 35 events/1000 subjects in the higher-risk group and 6 events/1000 subjects in the lower-risk group. With vaccination, these event rates dropped by 15 events/1000 subjects and 2 events/1000 subjects, respectively. This prediction rule may be a useful tool to complement other age-based strategies, to further encourage vaccination, especially among those at the highest risk of serious complications due to influenza. [ABSTRACT FROM AUTHOR]

A substudy analysis was conducted to determine the clinical characteristics associated with symptomatic, laboratory-documented influenza (LDI) among 2215 veterans with chronic obstructive pulmonary disease who participated in Department of Veterans Affairs Cooperative Study 448 and who received trivalent inactivated influenza virus vaccine with or without intranasal live-attenuated, cold-adapted influenza vaccine. Of 585 evaluable first occurrences of acute respiratory illnesses, 94 (16%) were LDI. Respiratory symptoms of cough, sputum production, and dyspnea occurred in >90% of patients with LDI; 68% had documented or subjective fever, and 81% had myalgias. Stepwise logistic regression identified only fever and myalgia as being statistically associated with LDI. During the influenza outbreak period, the positive predictive value of fever and myalgia was 41%. Clinical criteria were poor predictors of LDI in these older, vaccinated patients with chronic lung disease. Additional studies are warranted to define optimal methods for the diagnosis of influenza among older persons with chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

This serial cohort study assessed the risk of hospitalization or death associated with influenza and the effectiveness of influenza vaccination among subgroups of elderly members of 3 managed-care organizations in the United States. Data on baseline characteristics and outcomes were obtained from computerized databases. A total of 122,974 (1996-1997 season) and 158,454 (1997-1998 season) persons were included in the cohorts. Among unvaccinated persons, hospitalizations for pneumonia/influenza or death occurred in 8.2 of 1000 healthy and 38.4 of 1000 high-risk persons in year 1, and in 8.2 of 1000 healthy and 29.3 of 1000 high-risk persons in year 2. After adjustments, vaccination was associated with a 48% reduction in the incidence of hospitalization or death (95% confidence interval [CI], 42-52) in year 1 and 31% (95% CI, 26-37) in year 2. Effectiveness estimates were statistically significant and generally consistent across the healthy and high-risk subgroups. The absolute risk reduction, however, was 2.4- to 4.7-fold higher among high-risk than among healthy elderly persons. All elderly individuals may substantially benefit from vaccination. However, the impact of influenza is greater in persons with high-risk medical conditions. [ABSTRACT FROM AUTHOR]

In this article, the author comments on the studies of S. B. Manoff and D. M. Musher that was published in the February 15, 2010 issue of the journal. She believes that Musher's research furnishes new information on the duration and magnitude of the antibody after undergoing vaccination with PPSV23 in middle-aged and elderly adults. Moreover, she adds that Manoff's research is also significant because it details the results of immune response to PPSV23.