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Benefits of Influenza Vaccination for Low-, Intermediate-, and High-Risk Senior Citizens
Kristin L. Nichol, MD, MPH;
J. Wuorenma, RN, BSN;
T. von Sternberg, MD
Arch Intern Med. 1998;158:1769-1776.
ABSTRACT
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Background Vaccination rates for healthy senior citizens are lower than those for senior citizens with underlying medical conditions such as chronic heart or lung disease. Uncertainty about the benefits of influenza vaccination for healthy senior citizens may contribute to lower rates of utilization in this group.
Objective To clarify the benefits of influenza vaccination among low-risk senior citizens while concurrently assessing the benefits for intermediate- and high-risk senior citizens.
Methods All elderly members of a large health maintenance organization were included in each of 6 consecutive study cohorts. Subjects were grouped according to risk status: high risk (having heart or lung disease), intermediate risk (having diabetes, renal disease, stroke and/or dementia, or rheumatologic disease), and low risk. Outcomes were compared between vaccinated and unvaccinated subjects after controlling for baseline demographic and health characteristics.
Results There were more than 20000 subjects in each of the 6 cohorts who provided 147,551 person-periods of observation. The pooled vaccination rate was 60%. There were 101619 person-periods of observation for low-risk subjects, 15482 for intermediate-risk, and 30450 for high-risk subjects. Vaccination over the 6 seasons was associated with an overall reduction of 39% for pneumonia hospitalizations (P<.001), a 32% decrease in hospitalizations for all respiratory conditions (P<.001), and a 27% decrease in hospitalizations for congestive heart failure (P<.001). Immunization was also associated with a 50% reduction in all-cause mortality (P<.001). Within the risk subgroups, vaccine effectiveness was 29%, 32%, and 49% for high-, intermediate-, and low-risk senior citizens for reducing hospitalizations for pneumonia and influenza (for high and low risk, P .002; for intermediate risk, P =.11). Effectiveness was 19%, 39%, and 33% (for each, P .008), respectively, for reducing hospitalizations for all respiratory conditions and 49%, 64%, and 55% for reducing deaths from all causes (for each, P<.001). Vaccination was also associated with direct medical care cost savings of $73 per individual vaccinated for all subjects combined (P=.002). Estimates of cost savings within each risk group suggest that vaccination would be cost saving for each subgroup (range of cost savings of $171 per individual vaccinated for high risk to $7 for low risk), although within the subgroups these findings did not reach statistical significance (for each, P .05).
Conclusions This study confirms that healthy senior citizens as well as senior citizens with underlying medical conditions are at risk for the serious complications of influenza and benefit from vaccination. All individuals 65 years or older should be immunized with this vaccine.
INTRODUCTION
INFLUENZA IS a major cause of illness, suffering, and death in the United States and worldwide. Each year 10% to 20% of the US population becomes ill.1 Individuals aged 65 years or older are particularly susceptible to the complications of influenza, experiencing more than 90% of these complications that may include not only pneumonia but also exacerbations of underlying medical conditions such as chronic heart and lung disease2-4 and even death. In the United States, this burden includes hundreds of thousands of excess hospitalizations,1, 5 tens of thousands of excess deaths,3-4,6and billions of dollars in health care costs.7
Annual vaccination is recommended as the mainstay of efforts to prevent influenza for the elderly by the Advisory Committee on Immunization Practices of the US Public Health Service,8the American College of Physicians,9 and others. The World Health Organization10 has also suggested that elderly individuals be targeted for immunization. Despite these recommendations, influenza vaccine is underused. In the United States, 40% to 50% or more of targeted individuals fail to receive the vaccine each season.11-12 Worldwide underuse of influenza vaccine is also observed.13-14
Among the elderly, individuals with underlying medical conditions such as cardiopulmonary disease are at especially high risk for the serious complications of influenza.5, 15-17 There is widespread consensus regarding the importance of vaccination for this group.13 Patients and providers may be less convinced of the benefits of influenza vaccination for low-risk senior citizens. Uncertainty about the risks of influenza and benefits of vaccination for healthy elderly individuals may result in health care providers less frequently recommending vaccination for this group or in patients less frequently accepting the vaccine.18-20 This may in part explain why in the United States, vaccination rates are lower for elderly individuals without underlying conditions than they are for high-risk elderly individuals.21 Results from the 1994 National Health Interview Survey, for example, showed that the vaccination rate of elderly individuals with heart disease was 67.5% vs a rate of 51.7% for individuals without heart disease; the vaccination rate for elderly individuals with chronic lung disease was 71.2% vs 56.6% for individuals without lung disease (Centers for Disease Control and Prevention, Atlanta, Ga, unpublished data, December 1997). Uncertainty about the benefits of vaccination may also partially account for the considerable international variation in influenza vaccination recommendations and policies and incomplete agreement regarding the merits of age-based policies that recommend routine immunization for all elderly individuals.13
Few studies have assessed the benefits of influenza vaccination among senior citizens while differentiating subjects according to risk category. A placebo-controlled trial in the Netherlands conducted among low-risk senior citizens demonstrated that vaccination was associated with a 58% reduction in clinical and serologic influenza.22 A serial case-control study conducted over 9 seasons in the 1980s showed that influenza vaccination was associated with significant reductions in hospitalizations for pneumonia and influenza among both high-risk and low-risk senior citizens.23 However, while vaccination was cost saving among high-risk senior citizens, vaccination did not produce net direct medical care cost savings among the low-risk senior citizens. An earlier study24 in the same health care organization demonstrated significant reductions in hospitalizations for pneumonia during an epidemic season for high-risk senior citizens, but did not show a benefit for senior citizens without underlying cardiopulmonary disease. We conducted this study to further clarify the benefits of influenza vaccination for low-risk senior citizens while concurrently documenting the benefits for intermediate- and high-risk senior citizens from the same population and over the same period.
SUBJECTS AND METHODS
GROUP HEALTH SERIAL COHORT STUDIES: SETTING AND SUBJECTS
Group Health Inc is a staff model health maintenance organization with more than 300000 members in the Minneapolis and St Paul area, Minn. It has 21 clinics and 350 salaried physicians. In 1992 Group Health Inc became affiliated with HealthPartners Inc, a parent company providing integrated health care in coordination with several health care plans and administrative services.
Beginning with the 1989 influenza vaccination season, Group Health Inc piloted a modified version of the Minneapolis Veterans Affairs Medical Center influenza vaccination program,25and in 1990 the program was implemented in all the Group Health Inc clinics.26 This highly successful program has achieved and sustained vaccination rates in excess of 60% for elderly members of the plan. Previously, we reported on the health and economic benefits associated with influenza vaccination of all elderly members of this managed care organization for the years 1990-1991 through 1992-1993.27 We continued to conduct cohort studies for 3 additional seasons, 1993-1994 through 1995-1996, using methods similar to those in our original study. These new data pooled with the original 3 years of data collection now provide a database with consistent data elements and 147,551 person-periods of observation for the elderly members of this managed care organization. This study represents one of a series of studies assessing the impact of vaccine-preventable diseases and benefits of vaccination among the members of this managed care organization.
All members of the staff model plan were included in the cohort for the respective study season if they were 65 years or older on October 1 for the study year (the beginning of the vaccination season) and if they were enrolled continuously throughout both the vaccination season (October through December) and subsequent influenza season (the outcome period).
INFLUENZA SEASONS (OUTCOME PERIODS)
As with the first 3 years of the project, for the fourth through sixth seasons, the dates of the influenza seasons were selected based on surveillance information obtained from the Minnesota Department of Health.28-30 This influenza surveillance system includes information from passive reporting of school and nursing home outbreaks as well as laboratory identification of influenza isolates from specimens sent to the Minnesota Department of Health laboratories. The information collected is used to estimate both the level of influenza activity in the state as well as the type of influenza viruses circulating for a given season. The dates of first isolates were similar for these 3 years (November 11, 1993, November 28, 1994, and November 15, 1995), and we selected November 15 as the starting date for each season. For each season, 85% to 100% of all influenza isolates were obtained on or before April 1. To be consistent with our original study, we therefore defined the end of each season as March 31. In all cases, the dates of the influenza seasons included the total period of peak activity for each year.
DATA COLLECTION
All study data were obtained from the linked, administrative databases of Group Health Inc. Baseline information for the study subjects included demographic characteristics as well as information on prior health care utilization and previous outpatient and inpatient diagnoses listed in the databases. The specific diagnoses and their associated codes from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM)31 are as follows: heart disease (ICD-9-CM codes 393-398, 410-414, 425, 428, 429), lung disease (ICD-9-CM codes 491-496, 500-518), diabetes mellitus (ICD-9-CM code 250), chronic renal disease (ICD-9-CM codes 581, 582, 585, plus code 39.95 for dialysis from Current Procedural Terminology, Fourth Revision [CPT4]),32rheumatologic disease (ICD-9-CM codes 446, 710, 714), and dementia or stroke (ICD-9-CM codes 290-294, 331, 340, 341, 348, 438). These diagnoses were selected because they are associated with a higher risk for developing influenza-associated complications. Information on the receipt of pneumococcal vaccine during the previous 12 months (CPT4 code 907.32) and influenza vaccination status for the study season (CPT4 code 907.24) was also collected.
Subjects were also grouped into mutually exclusive categories according to their risk status. High risk was defined as having a baseline diagnosis of heart or lung disease. Intermediate risk was defined as having a baseline diagnosis of diabetes, renal disease, rheumatologic disease, or dementia and/or stroke, but not having underlying heart or lung disease. Low risk was defined as having none of these baseline diagnoses.
The primary outcomes were hospitalizations for pneumonia and influenza (ICD-9-CM codes 480-487) and deaths from any cause. Secondary outcomes included hospitalizations for all respiratory conditions (ICD-9-CM codes 460,462, 465, 466, 480-487, 500-518), hospitalizations for congestive heart failure (ICD-9-CM code 428), and hospitalization costs for all respiratory conditions and congestive heart failure combined. The diagnostic categories for the outcomes were selected to be consistent with previously identified categories of complications of influenza. Hospitalization costs reflected the charges submitted for each hospitalization episode.
STATISTICAL ANALYSIS
Bivariate comparisons for vaccinated and unvaccinated subjects were conducted using Student t tests and  2 tests for continuous and categorical variables, respectively. For the multivariate analyses, the units of analysis were person-periods of observation. Multivariate analyses comparing outcomes between the 2 groups while controlling for covariates and potential confounders were conducted using general linear (analysis of covariance) and logistic regression analysis models (SPSS for Windows 95, version 7.5, SPSS Inc, Chicago, Ill). Variables included in the models were age; sex; vaccination status; baseline diagnoses of heart disease, lung disease, diabetes, renal disease, rheumatologic disease, or stroke and/or dementia; number of previous hospitalizations and physicians' visits; and history of pneumonia. For those analyses specific to risk categories, the relevant baseline diagnoses were excluded from the models. Vaccine effectiveness was calculated as the percentage reduction in outcomes among vaccinated subjects compared with unvaccinated subjects. Mortality reduction among vaccine recipients was calculated from the results of the logistic regression analysis. Because the outcome events were rare, the adjusted odds ratio was used as an approximation of the relative risk. Thus, mortality reduction was calculated as (1 - odds ratio) x 100%. Cost savings associated with vaccination were calculated from the institution's perspective as direct savings associated with vaccination by comparing hospitalization costs between vaccinated and unvaccinated subjects. After subtracting the costs of the vaccination program (including vaccine, supplies, and administration costs), the difference in mean costs for vaccinated and unvaccinated subjects was then calculated.
RESULTS
There were more than 20000 subjects in each of the 6 cohorts who provided a total of 147,551 person-periods of observation. The overall vaccination rate was 60%. The baseline characteristics of the subjects are shown in Table 1. Vaccinated subjects were generally more likely than unvaccinated subjects to be male, to have baseline risk conditions such as underlying heart or lung disease, to have received pneumococcal vaccine in the previous year, and to have higher rates of resource utilization such as physician visits. Unvaccinated subjects, on the other hand, were more likely to have a history of dementia or stroke. There were 101619 subjects in the low-risk group (68.9%), 15482 in the intermediate-risk group (10.5%), and 30450 in the high-risk group (20.6%). The influenza vaccination rates for each group were 56%, 64%, and 69%, respectively.
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Table 1. Baseline Characteristics of Study Subjects
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The characteristics of the 6 influenza seasons and the numbers of outcomes are shown in Table 2. Influenza activity exceeded the epidemic threshold for 2 or more consecutive weeks for all the seasons except 1990-1991.33-37 There was a good to excellent match between vaccine and circulating virus strains each year with the exception of 1992-1993 when the match for the A/H3N2 component was poor (N. Cox, PhD, Centers for Disease Control and Prevention, written communication, February 1997). Over the 6 seasons, there were a total of 1010 hospitalizations for pneumonia and influenza, 4125 hospitalizations for all respiratory conditions, 1615 hospitalizations for congestive heart failure, and 1345 deaths.
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Table 2. Characteristics of Influenza Seasons and Study Outcomes*
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The estimates of vaccine effectiveness for hospitalizations and death for all elderly subjects by season are shown in Figure 1. Vaccine effectiveness was remarkably consistent over the 6 years. On average (Table 3), vaccination was associated with a 39% reduction in hospitalizations for pneumonia and influenza (P<.001), a 32% decrease in hospitalizations for all respiratory conditions (P<.001), and a 27% decrease in hospitalizations for congestive heart failure (P<.001). Immunization was also associated with a 50% reduction in deaths from all causes (P<.001).
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Figure 1. Influenza vaccine effectiveness over 6 consecutive seasons: reductions in hospitalizations for pneumonia and influenza (P&I) (A), all respiratory conditions (B), and congestive heart failure (CHF) (C), and in reducing deaths from all causes (D). Shown are the point estimates for effectiveness along with the 95% confidence interval. Values to the right of 0 indicate that vaccination reduces outcome event rates; to the left of 0, vaccination increases outcome event rates; and ACRC, all acute and chronic respiratory conditions. Data for 1990-1991 through 1992-1993 have been adapted from Nicholson et al.13 For the pooled estimates, data for 1990-1991 through 1995-1996 have been combined to provide 147,551 person-periods of observation.
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Table 3. Effectiveness of Influenza Vaccination in Reducing Primary and Secondary Outcomes Among Higher-Risk and Lower-Risk Subjects*
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The intermediate- and high-risk categories were associated with increasing rates of the study outcomes when compared with low-risk subjects. Adjusted odds ratios for intermediate- and high-risk subjects, respectively, for the primary study outcomes were 1.56 (95% confidence interval [CI], 1.23-2.02) and 3.26 (95% CI, 2.76-3.86) for any hospitalization for pneumonia and influenza, and 2.67 (95% CI, 2.26-3.16) and 3.33 (95% CI, 2.90-3.82) for all-cause mortality. For the secondary outcomes, the adjusted odds ratios for intermediate- and high-risk subjects were 1.52 (95% CI, 1.31-1.78) and 4.76 (95% CI, 4.30-5.23) for any hospitalization for acute and chronic respiratory disease, and 2.55 (95% CI, 1.98-3.29) and 10.32 (95% CI, 8.70-12.23) for any hospitalization for congestive heart failure. Because of the large numbers of subjects in the low-risk category, however, the numbers of outcomes in this group were substantial: 32% of the hospitalizations for pneumonia and influenza, 30% of the deaths, 26% of hospitalizations for all respiratory conditions, and 16% of hospitalizations for congestive heart failure.
The results of the analyses assessing vaccine effectiveness by risk group are shown in Table 3. High-risk subjects had the highest event rates and largest absolute reductions in events when vaccinated. However, all the groups benefited from vaccination with fewer hospitalizations for pneumonia and influenza and for all respiratory conditions, and with fewer deaths from all causes; estimates of vaccine effectiveness were similar across the groups for these outcomes (Figure 2). The benefits of vaccination were less consistent across the risk groups with regard to hospitalizations for congestive heart failure; vaccination was most strongly associated with fewer episodes among the high-risk subjects.
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Figure 2. Influenza vaccine effectiveness among low-, intermediate-, and high-risk subjects. The risk categories are as defined in the "Methods" section. Values to the right of 0 indicate that vaccination reduces outcome event rates; to the left of 0, vaccination increases outcome event rates; P & I, pneumonia and influenza; ACRC, all acute and chronic respiratory conditions; and CHF, congestive heart failure.
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Hospitalization costs for respiratory conditions and congestive heart failure over the 6 seasons were lower among all vaccinated subjects by $78 (95% CI, $27-$128; P=.002) (Table 3). After subtracting the costs of the vaccination program, the net savings associated with influenza vaccination were $73 per person vaccinated for all subjects combined. The point estimates for the net savings per person vaccinated by risk category were $166 for high-risk subjects, $117 for intermediate-risk subjects, and $7 for low-risk subjects (for individual risk groups, P.05).
COMMENT
Age-based strategies targeting all elderly individuals are more effective than risk disease–based strategies.38 In this study, we have provided further evidence supporting such strategies by showing that the benefits of influenza vaccination extended to all elderly subjects regardless of risk category. Over the 6-year period, vaccination of low as well as intermediate- and high-risk senior citizens was associated with significant reductions in complications of influenza such as hospitalizations for pneumonia and influenza and respiratory conditions and with fewer deaths from all causes.
Consistent with the findings of other investigators, subjects in our study who had a diagnosis of cardiac or pulmonary disease were at substantially increased risk for hospitalization and death when compared with subjects in the low-risk group.5, 15-17 While this high-risk group represented only 20.6% of all subjects in the study, they experienced 56% of the hospitalizations for pneumonia and 53% of the deaths. Nevertheless, intermediate- and low-risk senior citizens also experienced significant numbers of complications of influenza—a finding with significant public health implications. All groups benefited from vaccination.
The benefits of vaccination in our study extended not only to improved health but also to lower direct medical care costs. For all risk groups combined, the net cost savings were $73 per person vaccinated. Vaccination also appeared to be cost saving within each risk group with point estimates of net savings from $166 for high-risk subjects to $7 for low-risk subjects, although these estimates did not reach statistical significance because of the substantial variations within the subgroups. Other investigators have also found that influenza vaccination of the elderly results in direct medical cost savings for the influenza season23, 39-43 and that it is highly cost-effective per year of life saved when compared with other diagnostic or therapeutic interventions.43-45 In 1 study, however, investigators23 compared hospitalization costs for pneumonia between high- and low-risk subjects and found that vaccination of high but not low-risk subjects was associated with direct medical care cost savings. Our findings may differ from that study in part because of the broader range of outcomes included in the cost analysis.
This study provides additional evidence that the impact of influenza and benefits of vaccination for the elderly span a wide range of health outcomes, including hospitalization for pneumonia and influenza, all respiratory conditions, and death.2-6,46 Vaccination was also associated with fewer hospitalizations for congestive heart failure, although this association was strongest for high-risk subjects, many of whom had preexisting cardiac disease. The magnitude of reduction in the outcomes among vaccinated subjects also provides indirect evidence that influenza is directly or indirectly responsible for a large percentage of these events during the influenza season; this held true for low- as well as intermediate- and high-risk subjects. For all senior citizens, the influenza-attributable proportion of these outcomes is undoubtedly substantial but frequently unapparent and unrecognized.
Studies in other populations have highlighted the health benefits associated with influenza vaccination of community-dwelling senior citizens. A placebo-controlled trial22from the Netherlands confirmed that vaccination reduced clinical and serologic influenza illness among the elderly by 58%. Observational studies39-50 from the United States, Canada, and the United Kingdom have demonstrated that vaccination is associated with lower rates of complications of influenza such as hospitalization for pneumonia and influenza and for pneumonia together with other respiratory conditions.47, 50 Several studies have also shown lower death rates from all causes47, 51or from influenza.52 A recent meta-analysis has confirmed the benefits of vaccination for elderly residents of long-term care facilities with significant reductions in respiratory illness, hospitalization, and death.53 Most of these studies evaluated the benefits of vaccination over 1 or 2 seasons and included fewer outcomes than were evaluated in this study. In our study, we have shown how the benefits of vaccination can also be consistent and substantial over multiple, consecutive seasons.
Strengths of this study include the large study population, inclusion of multiple, consecutive seasons, and the use of the cohort design, the strongest design for observational or noninterventional studies. We also collected information on baseline risk characteristics to adjust for differences in risk factors between vaccinated and unvaccinated subjects and to identify the independent contribution of vaccination to the occurrence of outcome events. Nevertheless, a limitation of all observational studies is the difficulty in performing adequate risk adjustment in the multivariate analyses.54 In the absence of randomization, it is always possible that there were significant, unmeasured differences between the comparison groups that may have influenced the study findings and conclusions. Misclassification of vaccination status may also have occurred in this study, most likely because of incomplete recording in the administrative databases. However, we have previously shown that the Group Health Inc databases are highly accurate in capturing influenza vaccination status, with 93% agreement between medical records and the computerized databases (K.L.N., unpublished data, September 1995). Furthermore, even if misclassification occurred to any significant extent, this most likely would have biased the study findings to a negative conclusion.
CONCLUSIONS
Millions of elderly individuals fail to receive influenza vaccine each year. Our study confirms that healthy senior citizens as well as senior citizens with underlying medical conditions suffer the serious complications of influenza and that they benefit substantially from vaccination. All individuals aged 65 years or older should be immunized with this vaccine.
AUTHOR INFORMATION
Accepted for publication January 20, 1998.
This study was supported in part by grants from Connaught Laboratories, Swiftwater, Pa, and Pasteur Merieux Connaught, Lyon, France.
We thank Andrew Nelson, MPH, for his support of these efforts.
Reprints: Kristin L. Nichol, MD, MPH, Medicine Service (111), Veterans Affairs Medical Center, 1 Veterans Dr, Minneapolis, MN 55417.
From the Medicine Service, Veterans Affairs Medical Center, and University of Minnesota, Minneapolis (Dr Nichol), and HealthPartners Inc, Bloomington, Minn (Ms Wuorenma and Dr Sternberg).
REFERENCES
| |
1. Couch RB. Advances in influenza virus vaccine research. Ann N Y Acad Sci. 1993;685:803-812.
WEB OF SCIENCE
| PUBMED
2. McBean AM, Babish JD, Warren JL. The impact and cost of influenza in the elderly. Arch Intern Med. 1993;153:2105-2111.
FREE FULL TEXT
3. Lui K, Kendal AP. Impact of influenza epidemics on mortality in the United States from October 1972 to May 1985. Am J Public Health. 1987;77:712-716.
FREE FULL TEXT
4. Glezen WP. Serious morbidity and mortality associated with influenza epidemics. Epidemiol Rev. 1982;4:25-44.
FREE FULL TEXT
5. Barker WH. Excess pneumonia and influenza associated hospitalization during influenza epidemics in the United States, 1970-78. Am J Public Health. 1986;76:761-765.
FREE FULL TEXT
6. Collins SD, Lehmann J. Excess Deaths From Chronic Disease During Influenza Epidemics. Washington, DC: US Government Printing Office; 1953:1-21. US Public Health Service publication 213.
7. Williams WW, Hickson MA, Kane MA, et al. Immunization policies and vaccine coverage among adults: the risk for missed opportunities. Ann Intern Med. 1988;108:616-625.
8. Centers for Disease Control and Prevention. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 1997;46(RR-9):1-25.
9. American College of Physicians. Guide for Adult Immunization. 3rd ed. Philadelphia, Pa: American College of Physicians; 1994:90-96.
10. World Health Organization. WHO announces influenza vaccine formula for 1997/1998: press release WHO/14. Available at: http://www.who.ch/. Accessed February 20, 1997.
11. Centers for Disease Control and Prevention. Influenza and pneumococcal vaccination coverage levels among persons aged 65 years: United States, 1973-1993. MMWR Morb Mortal Wkly Rep. 1995;44:506-507, 513-515.
PUBMED
12. Centers for Disease Control and Prevention. Assessing adult vaccination status at age 50 years. MMWR Morb Mortal Wkly Rep. 1995;44:561-563.
PUBMED
13. Nicholson KG, Snacken R, Palache AM. Influenza immunization policies in Europe and the United States. Vaccine. 1995;13:365-369.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
14. Fedson DS, Hirota Y, Shin HK, et al. Influenza vaccination in 22 developed countries: an update to 1995. Vaccine. 1997;15:1506-1511.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
15. Glezen WP, Decker M, Perrotta DM. Survey of underlying conditions of persons hospitalized with acute respiratory disease during influenza epidemics in Houston, 1978-1981. Am Rev Respir Dis. 1987;136:550-555.
WEB OF SCIENCE
| PUBMED
16. Foster DA, Talsma A, Furumoto-Dawson A, et al. Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly. Am J Epidemiol. 1992;136:296-307.
FREE FULL TEXT
17. Ohmit SE, Monto AS. Influenza vaccine effectiveness in preventing hospitalization among the elderly during influenza type A and type B seasons. Int J Epidemiol. 1995;24:1240-1248.
FREE FULL TEXT
18. Larson EB, Olsen E, Cole W, Shortell S. The relationship of health beliefs and a postcard reminder to influenza vaccination. J Fam Pract. 1979;8:1207-1211.
WEB OF SCIENCE
| PUBMED
19. Riddiough MA, Willems JS, Sanders CF, Kemp K. Factors affecting the use of vaccines: considerations for immunization program planners. Public Health Rep. 1981;96:528-535.
WEB OF SCIENCE
| PUBMED
20. Buffington J, LaForce FM. Achievable influenza immunization rates in the elderly. N Y State J Med. 1991;91:433-435.
WEB OF SCIENCE
| PUBMED
21. Gillick MR, Ditzion B. Influenza vaccination: are we doing better than we think? Arch Intern Med. 1991;151:1742-1744.
FREE FULL TEXT
22. Govaert Th ME, Thijs CTMCN, Masurel N, et al. The efficacy of influenza vaccination in elderly individuals: a randomized double-blind placebo-controlled trial. JAMA. 1994;272:1661-1665.
FREE FULL TEXT
23. Mullooly JP, Bennett MD, Hornbrook MC, et al. Influenza vaccination programs for elderly persons: cost-effectiveness in a health maintenance organization. Ann Intern Med. 1994;121:947-952.
FREE FULL TEXT
24. Barker WH, Mullooly JP. Influenza vaccination of elderly persons: reduction in pneumonia and influenza hospitalizations and deaths. JAMA. 1980;244:2547-2549.
FREE FULL TEXT
25. Nichol KL. Long-term success with the national health objective for influenza vaccination: an institution-wide model. J Gen Intern Med. 1992;7:595-600.
WEB OF SCIENCE
| PUBMED
26. Margolis KL, Nichol KL, Wuorenma J, von Sternberg TL. Exporting a successful influenza vaccination program from a teaching hospital to a community outpatient setting. J Am Geriatr Soc. 1992;40:1021-1023.
WEB OF SCIENCE
| PUBMED
27. Nichol KL, Margolis KL, Wuorenma J, von Sternberg T. The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community. N Engl J Med. 1994;331:778-784.
FREE FULL TEXT
28. Minnesota Dept of Health. Annual summary of communicable diseases reported to the Minnesota Department of Health, 1993. Dis Control Newslett. 1994;22:25-36.
29. Minnesota Dept of Health. Annual summary of communicable diseases reported to the Minnesota Department of Health, 1994. Dis Control Newslett. 1995;23:32-43.
30. Minnesota Dept of Health. Annual summary of communicable diseases reported to the Minnesota Department of Health, 1995. Dis Control Newslett. 1996;24:25-40.
31. International Classification of Diseases, Ninth Revision, Clinical Modification. Washington, DC: Public Health Service, US Dept of Health and Human Services; 1988.
32. Physicians' Current Procedural Terminology. Chicago, Ill: American Medical Association; 1997.
33. Centers for Disease Control and Prevention. Influenza surveillance: United States, 1989-90 and 1990-91 seasons. MMWR CDC Surveill Summ. 1992;41(SS-3):35-46.
34. Centers for Disease Control and Prevention. Influenza surveillance: United States, 1991-92. MMWR CDC Surveill Summ. 1992;41(SS-5):35-46.
35. Centers for Disease Control and Prevention. Influenza surveillance: United States, 1992-93 and 1993-94. MMWR CDC Surveill Summ. 1997;46(SS-1):1-12.
36. Centers for Disease Control and Prevention. Update: influenza activity—United States and worldwide 1994-95 season, and composition of the 1995-96 influenza vaccine. MMWR Morb Mortal Wkly Rep. 1995;44:292-295.
PUBMED
37. Centers for Disease Control and Prevention. Update: influenza activity—United States and worldwide, 1995-96 season, and composition of the 1996-97 influenza vaccine. MMWR Morb Mortal Wkly Rep. 1996;45:326-329.
PUBMED
38. Honkanen PO, Keistinen T, Kivela SL. The impact of vaccination strategy and methods of information on influenza and pneumococcal vaccination coverage in the elderly population. Vaccine. 1997;15:317-320.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
39. Maucher JM, Gambert SR. Cost-effective analysis of influenza vaccination in the elderly. Age. 1990;13:3-9.
40. Centers for Disease Control and Prevention. Final results: Medicare influenza vaccine demonstration—selected states, 1988-1992. MMWR Morb Mortal Wkly Rep. 1993;42:601-604.
PUBMED
41. Helliwell BE, Drummond MF. The costs and benefits of preventing influenza in Ontario's elderly. Can J Public Health. 1988;79:175-179.
WEB OF SCIENCE
| PUBMED
42. Scott WG, Scott HM. Economic evaluation of vaccination against influenza in New Zealand. Pharm Econ. 1996;9:51-60.
43. Riddiough MA, Sisk JE, Bell JC. Influenza vaccination: cost-effectiveness and public policy. JAMA. 1983;249:3189-3195.
FREE FULL TEXT
44. Russell LB. Opportunity costs in modern medicine. Health Aff (Millwood). 1992;11:162-169.
PUBMED
45. Fedson DS. Influenza and pneumococcal vaccination of the elderly: newer vaccines and prospects for clinical benefits at the margin. Prev Med. 1994;23:751-755.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
46. Perrotta DM, Decher M, Glezen WP. Acute respiratory disease hospitalizations as a measure of impact of epidemic influenza. Am J Epidemiol. 1985;122:468-476.
FREE FULL TEXT
47. Fedson DS, Wajda A, Nicol JP, et al. Clinical effectiveness of influenza vaccination in Manitoba. JAMA. 1993;270:1956-1961.
FREE FULL TEXT
48. Foster DA, Talsma A, Furumoto-Dawson A, et al. Influenza vaccine effectiveness in preventing hospitalization for pneumonia in the elderly. Am J Epidemiol. 1992;136:296-307.
49. Ohmit SE, Monto AS. Influenza vaccine effectiveness in preventing hospitalization among the elderly during influenza type A and type B seasons. Int J Epidemiol. 1995;24:1240-1248.
50. Ahmed AH, Nicholson KG, Nguyen-Van Tam JS, Pearson JC. Effectiveness of influenza vaccination in reducing hospital admissions during the epidemic of 1989-90. Epidemiol Infect. 1997;118:27-33.
FULL TEXT
| PUBMED
51. Fleming DM, Watson JM, Nicholas S, et al. Study of the effectiveness of influenza vaccination in the elderly in the epidemic of 1989-90 using a general practice database. Epidemiol Infect. 1995;115:581-589.
PUBMED
52. Ahmed AEH, Nicholson KG, Nguyen-Van Tam JS. Reduction in mortality associated with influenza vaccine during 1989-90 epidemic. Lancet. 1995;346:591-595.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
53. Gross PA, Hermogenes AW, Sacks HS, et al. The efficacy of influenza vaccine in elderly persons: a meta-analysis and review of the literature. Ann Intern Med. 1995;123:518-527.
FREE FULL TEXT
54. Iezzoni LI. Risk and outcomes. In: Iezzoni LI, ed. Risk Adjustment for Measuring Health Care Outcomes. Ann Arbor, Mich: Health Administration Press; 1994:1-28.
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Cost-effectiveness analysis of influenza and pneumococcal vaccination for Hong Kong elderly in long-term care facilities
You et al.
J. Epidemiol. Community Health 2009;63:906-911.
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Effects of annual influenza vaccination on winter mortality in elderly people with chronic heart disease
de Diego et al.
Eur Heart J 2009;30:209-216.
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Influenza Vaccination in Adolescents With High-Risk Conditions
Nakamura and Lee
Pediatrics 2008;122:920-928.
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Influenza-Associated Pediatric Mortality in the United States: Increase of Staphylococcus aureus Coinfection
Finelli et al.
Pediatrics 2008;122:805-811.
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Rectification of Age-Associated Deficiency in Cytotoxic T Cell Response to Influenza A Virus by Immunization with Immune Complexes
Zheng et al.
J. Immunol. 2007;179:6153-6159.
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Effectiveness of Influenza Vaccine in the Community-Dwelling Elderly
Nichol et al.
NEJM 2007;357:1373-1381.
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Influenza Vaccination: An Unmet Need in Patients With Diabetes
Schaffner et al.
Clin. Diabetes 2007;25:145-149.
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Mortality Trends in Men and Women with Diabetes, 1971 to 2000
Gregg et al.
ANN INTERN MED 2007;147:149-155.
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Long-standing influenza vaccination policy is in accord with individual self-interest but not with the utilitarian optimum
Galvani et al.
Proc. Natl. Acad. Sci. USA 2007;104:5692-5697.
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Live Attenuated Influenza Virus Expressing Human Interleukin-2 Reveals Increased Immunogenic Potential in Young and Aged Hosts
Ferko et al.
J. Virol. 2006;80:11621-11627.
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Annual influenza vaccination in community-dwelling elderly individuals and the risk of lower respiratory tract infections or pneumonia.
Voordouw et al.
Arch Intern Med 2006;166:1980-1985.
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Influenza Vaccination as Secondary Prevention for Cardiovascular Disease: A Science Advisory From the American Heart Association/American College of Cardiology
Davis et al.
J Am Coll Cardiol 2006;48:1498-1502.
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Influenza Vaccination as Secondary Prevention for Cardiovascular Disease: A Science Advisory From the American Heart Association/American College of Cardiology: Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, the American Association of Critical Care Nurses, the American Association of Heart Failure Nurses, the American Diabetes Association, the Association of Black Cardiologists, Inc., the Heart Failure Society of America, and the Preventive Cardiovascular Nurses Association.: The American Academy of Nurse Practitioners supports the recommendations of this scientific advisory.: This science advisory is consistent with the recommendations of the Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices.
Davis et al.
Circulation 2006;114:1549-1553.
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Impact of a Winter Respiratory Virus Season on Patients With COPD and Association With Influenza Vaccination.
Gorse et al.
Chest 2006;130:1109-1116.
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Insights into the Interaction between Influenza Virus and Pneumococcus
McCullers
Clin. Microbiol. Rev. 2006;19:571-582.
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Hospitalization Trends for Pneumonia Among Older Persons--Reply
Fry and Shay
JAMA 2006;295:2138-2138.
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Evidence of bias in estimates of influenza vaccine effectiveness in seniors
Jackson et al.
Int J Epidemiol 2006;35:337-344.
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Functional status is a confounder of the association of influenza vaccine and risk of all cause mortality in seniors
Jackson et al.
Int J Epidemiol 2006;35:345-352.
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Trends in Hospitalizations for Pneumonia Among Persons Aged 65 Years or Older in the United States, 1988-2002
Fry et al.
JAMA 2005;294:2712-2719.
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Pneumonia in Older Adults: Reversing the Trend
File and Tan
JAMA 2005;294:2760-2763.
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Guidelines for the management of adult lower respiratory tract infections
Woodhead et al.
Eur Respir J 2005;26:1138-1180.
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Infectious Disease Hospitalizations Among Older Adults in the United States From 1990 Through 2002
Curns et al.
Arch Intern Med 2005;165:2514-2520.
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Generation of an Influenza A Virus Vector Expressing Biologically Active Human Interleukin-2 from the NS Gene Segment
Kittel et al.
J. Virol. 2005;79:10672-10677.
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Influenza Vaccination Among Diabetic Adults: Related factors and trend from 1993 to 2001 in Spain
Jimenez-Garcia et al.
Diabetes Care 2005;28:2031-2033.
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Impact of Influenza Vaccination on Seasonal Mortality in the US Elderly Population
Simonsen et al.
Arch Intern Med 2005;165:265-272.
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Clinical Effectiveness of Influenza Vaccination in Persons Younger Than 65 Years With High-Risk Medical Conditions: The PRISMA Study
Hak et al.
Arch Intern Med 2005;165:274-280.
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The Novel Parainfluenza Virus Hemagglutinin-Neuraminidase Inhibitor BCX 2798 Prevents Lethal Synergism between a Paramyxovirus and Streptococcus pneumoniae
Alymova et al.
Antimicrob. Agents Chemother. 2005;49:398-405.
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Prioritizing Influenza Vaccination
Rothberg
JAMA 2004;292:2582-2583.
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Reduced Hospitalizations and Death Associated With Influenza Vaccination Among Patients With and Without Diabetes
Heymann et al.
Diabetes Care 2004;27:2581-2584.
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National survey of the prevalence, incidence, primary care burden, and treatment of heart failure in Scotland
Murphy et al.
Heart 2004;90:1129-1136.
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Influenza-Associated Hospitalizations in the United States
Thompson et al.
JAMA 2004;292:1333-1340.
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Inhibition of influenza virus production in virus-infected mice by RNA interference
Ge et al.
Proc. Natl. Acad. Sci. USA 2004;101:8676-8681.
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Acute Respiratory Illness in Patients With COPD and the Effectiveness of Influenza Vaccination: A Randomized Controlled Study
Wongsurakiat et al.
Chest 2004;125:2011-2020.
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Additive preventive effect of influenza and pneumococcal vaccines in elderly persons
Christenson et al.
Eur Respir J 2004;23:363-368.
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The Business Case for Quality: Combining Medical Literature Research with Health Plan Data to Establish Value for Nonclinical Managers
Fetterolf and West
American Journal of Medical Quality 2004;19:48-55.
ABSTRACT
Influenza and Cardiovascular Disease: A New Opportunity for Prevention and the Need for Further Studies
Madjid et al.
Circulation 2003;108:2730-2736.
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Management of Influenza in Adults Older than 65 Years of Age: Cost-Effectiveness of Rapid Testing and Antiviral Therapy
Rothberg et al.
ANN INTERN MED 2003;139:321-329.
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Impact of Oseltamivir Treatment on Influenza-Related Lower Respiratory Tract Complications and Hospitalizations
Kaiser et al.
Arch Intern Med 2003;163:1667-1672.
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Addressing the Burden of Diabetes in the 21st Century: Better Care and Primary Prevention
Engelgau et al.
J. Am. Soc. Nephrol. 2003;14:S88-91.
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Conventional Influenza Vaccination Is Not Associated with Complications in Working-Age Patients with Asthma or Chronic Obstructive Pulmonary Disease
Hak et al.
Am J Epidemiol 2003;157:692-700.
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Influenza Vaccination and Reduction in Hospitalizations for Cardiac Disease and Stroke among the Elderly
Nichol et al.
NEJM 2003;348:1322-1332.
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Mortality Associated With Influenza and Respiratory Syncytial Virus in the United States
Thompson et al.
JAMA 2003;289:179-186.
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Confounding by indication in non-experimental evaluation of vaccine effectiveness: the example of prevention of influenza complications
Hak et al.
J. Epidemiol. Community Health 2002;56:951-955.
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Failure to Vaccinate Medicare Inpatients: A Missed Opportunity
Bratzler et al.
Arch Intern Med 2002;162:2349-2356.
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Hospitalizations and Deaths Due to Respiratory Illnesses During Influenza Seasons: A Comparison of Community Residents, Senior Housing Residents, and Nursing Home Residents
Menec et al.
Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2002;57:M629-635.
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A Diabetes Report Card for the United States: Quality of Care in the 1990s
Saaddine et al.
ANN INTERN MED 2002;136:565-574.
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Generalist and Subspecialist Physicians' Knowledge, Attitudes, and Practices Regarding Influenza and Pneumococcal Vaccinations for Elderly and Other High-Risk Patients: A Nationwide Survey
Nichol and Zimmerman
Arch Intern Med 2001;161:2702-2708.
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Quality Indicators for the Management of Pneumonia in Vulnerable Elders
Rhew
ANN INTERN MED 2001;135:736-743.
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Influenza: vaccination and treatment
Stephenson and Nicholson
Eur Respir J 2001;17:1282-1293.
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The Japanese Experience with Vaccinating Schoolchildren against Influenza
Reichert et al.
NEJM 2001;344:889-896.
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Chronic Obstructive Pulmonary Disease
Sethi et al.
NEJM 2000;343:1969-1971.
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Influenza: Prospects for Control
Couch
ANN INTERN MED 2000;133:992-998.
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Prevention and Treatment of Influenza
Couch
NEJM 2000;343:1778-1787.
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Comparison of Immunogenicity and Safety of a Virosome Influenza Vaccine with Those of a Subunit Influenza Vaccine in Pediatric Patients with Cystic Fibrosis
Schaad et al.
Antimicrob. Agents Chemother. 2000;44:1163-1167.
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The Health and Economic Benefits Associated With Pneumococcal Vaccination of Elderly Persons With Chronic Lung Disease
Nichol et al.
Arch Intern Med 1999;159:2437-2442.
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Relation between Influenza Vaccination and Outpatient Visits, Hospitalization, and Mortality in Elderly Persons with Chronic Lung Disease
Nichol et al.
ANN INTERN MED 1999;130:397-403.
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Influenza Vaccine for All Senior Citizens
JWatch Infect. Diseases 1998;1998:15-15.
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Flu Vaccine for Low-Risk Elderly Patients?
JWatch General 1998;1998:4-4.
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