Skip Navigation

Influence of High-Risk Medical Conditions on the Effectiveness of Influenza Vaccination among Elderly Members of 3 Large Managed-Care Organizations

  1. Eelko Hak1,6,
  2. James Nordin1,
  3. Feifei Wei1,
  4. John Mullooly3,
  5. Sung Poblete4,
  6. Raymond Strikas5, and
  7. Kristin L Nichol1,2
  1. 1HealthPartners Research Foundation, Bloomington
  2. 2Veterans Affairs Medical Center and University of Minnesota, Minneapolis
  3. 3Kaiser Permanente Northwest, Portland, Oregon
  4. 4Oxford Health Plans, New York, New York
  5. 5Centers for Disease Control and Prevention, Atlanta, Georgia
  6. 6Julius Center for General Practice and Patient Oriented Research, University Medical Center, Utrecht, The Netherlands
  1. Reprints or correspondence: Dr. Kristin L. Nichol, VA Medical Center (111), 1 Veterans Dr., Minneapolis, MN 55417 (nicho014{at}tc.umn.edu)
 
Next Section

Abstract

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

Annual epidemics of influenza continue to impose an enormous health and economic burden on society, especially among elderly persons [1, 2]. Vaccination against influenza has been demonstrated to be effective in reducing associated morbidity and mortality [3–6] and in saving costs among elderly individuals [7]. Despite evidence of its cost-effectiveness, however, current vaccination rates remain unsatisfactory. In the United States, for example, >30% of elderly individuals do not receive the vaccine each season [8]. Similarly low vaccine-uptake rates have been reported in other countries [9]. Apart from differences in health care, studies have shown that among the main reasons for compliance with vaccination recommendations are the recommendations of health care providers and understanding of the impact of influenza and the safety and effectiveness of the vaccine [10–12]

Underlying conditions, such as cardiopulmonary disease, are well-known risk factors for serious influenza-associated complications [3–6, 13, 14]. However, the clinical effectiveness of influenza vaccination among persons with specific chronic, high-risk medical conditions has not been well described, and this may lead to uncertainties regarding the benefits of vaccination in these groups of persons. On the other hand, data on the rates of serious complications of influenza in healthy elderly persons are limited and suggest that the impact is lower than that among elderly persons with high-risk disease [15, 16]. Two cohort studies published elsewhere were inconclusive with regard to benefits of vaccine for low-risk senior citizens [17, 18]. These findings may help explain the suboptimal vaccination rates in the elderly population, and they likely have contributed to widespread international variation in vaccination recommendations [19]

Age-based vaccination policies are attractive both from an organizational and a health-economic point of view. However, additional information that clarifies issues of individual risk for the serious complications of influenza and the benefits of vaccination may help policy makers and program planners design more-effective vaccination programs or to prioritize vaccine delivery when vaccine supplies are inadequate [20, 21]. Therefore, in a prospective cohort study that used the administrative and clinical databases of 3 managed-care organizations in the United States, we determined the occurrence of influenza/pneumonia hospitalizations and death due to all causes during the 1996–1997 and 1997–1998 influenza epidemics and the effectiveness of influenza vaccination in preventing these outcomes in specific high-risk subgroups of elderly plan members. These subgroups included persons with cardiopulmonary disease, diabetes, immunosuppression, and other high-risk diseases, as well as healthy elderly individuals

Previous SectionNext Section

Materials and Methods

Setting This study is part of an ongoing collaborative effort between 3 large managed-care organizations from geographically disparate locations across the United States to pool data derived from their linked administrative and clinical databases to provide timely assessments of influenza vaccination effectiveness. The results for the first 2 years of this collaborative effort for all elderly persons combined have been reported elsewhere [22]

HealthPartners (HP) is a nonprofit health maintenance organization (HMO) with ∼890,000 members in Minnesota and Wisconsin. It offers coverage for 280,000 members through a staff model HMO, whereas the other members are covered through a network HMO model. Kaiser Permanente Northwest Division (KPNW) provides health care services to nearly 420,000 persons in the Portland, Oregon and Vancouver, Washington area. Oxford Health Plans (Oxford) provide health benefit plans to 1.8 million members in New York, New Jersey, Pennsylvania, and Connecticut. In all, >3 million members receive medical care from these health plans. For study purposes, the same definitions of diagnoses and outcomes were used. Data were obtained for all elderly members of HP and KPNW, whereas, for Oxford, we collected only data on elderly members in the New York City metropolitan area and the adjacent counties

Study subjects Eligibility criteria to be included in the 2 study cohorts were as follows: membership in 1 of the 3 health plans, age of ⩾65 years (as of 1 October 1996 for the first year and 1 October 1997 for the second year), and continuous enrollment for the 1-year period before 1 October for each study year through the outcome period. The continuous enrollment period was required to ensure complete capture of outcome data and enough prognostic information to allow for the adjustment of potential incomparability between comparison groups [23]. Because of logistic considerations, for Oxford, data were collected only for members living in New York City and surrounding counties. For the other health plans, data were collected on all plan members who met the eligibility criteria. The health plans cover institutionalized persons (i.e., those who live in nursing homes) as well as community-dwelling persons. Because capture of vaccination status was thought to be incomplete for institutionalized people, data from these people were excluded from the study. For the 1996–1997 and 1997–1998 study years, there were 122,974 and 158,454 eligible plan members among the 3 health plans combined

At baseline, eligible subjects were classified into 7 non–mutually exclusive groups according to entries of relevant codes in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) in outpatient clinic or hospital databases 12 months before 30 September 1996 in year 1 and 30 September 1997 in year 2, as follows: (1) combination of pulmonary (ICD-9-CM codes 011, 460, 462, 465–466, 480–511, 512.8, 513–517, 518.3, 518.8, 519.9, and 714.81) and cardiac (ICD-9-CM codes 093, 112.81, 130.3, 391, 393–398, 402, 404, 410–429, 745–746, 747.1–747.49, 759.82, 785.2, and 785.3) disease, (2) pulmonary disease, (3) cardiac disease, (4) diabetes and other endocrine disorders (ICD-9-CM codes 250–251), (5) immunosuppression (renal disease [ICD-9-CM codes 274.1, 403, 580–591, 593.71–593.73, and 593.9], immunodeficiency or receipt of organ transplants [ICD-9-CM codes 042, 079, 279, V08, and V42], hematologic cancer [ICD-9-CM codes 200–208], or nonhematologic cancer [ICD-9-CM codes 140–198 and 199.1]), (6) other comorbid conditions (dementia or stroke [ICD-9-CM codes 290–294, 331, 340–341, 348, and 438], vasculitis, or rheumatologic diseases [ICD-9-CM codes 446, 710, 714–714.4, 714.8, 714.89, and 714.9]), and (7) being a healthy elderly individual (i.e., having none of the previously listed diagnostic codes in their records). Other baseline data that were obtained included age and sex, number of any hospitalizations or outpatient visits, and whether a person had been hospitalized for pneumonia/influenza during the previous year

Influenza vaccination and seasons The health plans offered their members vaccination with the trivalent inactivated influenza virus vaccine current for each season. During the 1996–1997 epidemic, influenza activity was widespread in most US states, exceeding baseline levels for >5 consecutive weeks. Circulating influenza strains predominated by the H3N2 A type matched well with the components of the vaccine of that year [24]. In 1997–1998, the level of influenza activity was similar, but another influenza A virus, the A/H3N2/Sydney-like virus, became the predominant strain in most areas in the United States [25]. That year's vaccine, which contained A/H3N2/Wuhan-like virus, was poorly matched to the predominant circulating virus. On the basis of regional and national influenza surveillance data from the Centers for Disease Control and Prevention (CDC), influenza seasons were defined as follows: for year 1: HP, 22 November 1996–24 May 1997; Oxford, 5 October 1996–3 May 1997; and KPNW, 22 November 1996–22 March 1997; and for year 2: HP, 7 December 1997–28 March 1998; Oxford, 23 November 1997–4 April 1998; and KPNW, 21 December 1997–7 March 1998. Influenza vaccination status was ascertained from the computerized databases of each managed-care organization

Primary outcome measure Excess hospitalizations and deaths during influenza seasons are strongly and linearly correlated [26]. As others have done [27], we used as our primary study outcome the combined outcome of a hospitalization for pneumonia/influenza (ICD-9-CM codes 480–487) or death. We used this combined outcome to enhance the power of our study and to provide more-precise estimates of vaccine effectiveness within the disease-based high-risk subgroups

Data analysis Each participating health plan center extracted data about eligible subjects from their linked databases and forwarded these data to the coordinating data-management center at HP. By use of EpiInfo, version 6 (CDC), we estimated that a minimal cohort size of 27,000 would give us an 85% chance of detecting a reduction of ⩾20% in outcome events among recipients of the influenza vaccine. For this calculation, we assumed an vaccination rate of 55%, an event rate of 3%, and a 2-sided α level of.05. Bivariate analysis, which was performed using SPSS for Windows, version 9.0 (SPSS), included Student's t tests for continuous and χ2 tests for categorical variables to test for differences between comparison groups. Multivariable logistic regression was used to assess the association of vaccination status with the study outcome measures while controlling for age, sex, comorbid medical conditions, prior health care use (hospitalizations and outpatient visits), and whether the person had previously been hospitalized for pneumonia/influenza. In addition, the site was also included in the models. For analyses by specific subgroups, the relevant underlying medical conditions were excluded from the model. Adjusted ORs and their 95% CIs (as approximations of relative risks) were calculated. Vaccine effectiveness (VE) was determined as 1 - OR × 100%. Absolute risk reductions per 1000 vaccinees (ARRs) were calculated as the VE times the outcome rate in unvaccinated persons. The number needed to treat (i.e., vaccinate) to save 1 outcome (NNT) was calculated as (1/ARR) × 1000 [28]

Previous SectionNext Section

Results

Data on 122,974 and 158,454 elderly persons were obtained for the 1996–1997 and 1997–1998 study years, respectively. The vaccination rates for all 3 sites combined were 57.7% in year 1 and 58.1% in year 2. For both years, vaccinated subjects were somewhat older and generally more likely to have high-risk medical conditions than were unvaccinated subjects (table 1). Vaccinated persons also had higher numbers of outpatient visits during the baseline period. Both groups had similar rates of hospitalization during the baseline period

Figure 1
Figure 1

Effectiveness of influenza vaccination for reducing pneumonia/influenza hospitalizations or deaths due to all causes among high-risk (HR) and healthy elderly individuals during the 1996–1997 (top) and 1997–1998 (bottom) influenza seasons. Shown are the estimates for vaccine effectiveness (calculated as 1 - adjusted OR) along with their 95% CIs. Ht, heart; Immune Supp., immunosuppression

Table 1
Table 1

Baseline characteristics of elderly subjects in a study of the effectiveness of influenza vaccine, according to study year

There were 1961 outcome events (i.e., hospitalizations for pneumonia/influenza or deaths) in year 1 and 2555 outcome events in year 2 (table 2). Unvaccinated persons had higher event rates than did vaccinated persons in each subgroup and for both years. Vaccination was associated with a reduction in the combined outcome of a hospitalization for pneumonia/influenza or death due to any cause of 48% (95% CI, 42–52) in year 1 and 31% (95% CI, 26–37) in year 2 (table 3). When analyzed according to subgroup, influenza vaccination was consistently effective across each of the disease-specific categories in both years as well as among the healthy subgroup (table 3, figure 1)

Table 2
Table 2

Numbers of outcome events among vaccinated and unvaccinated study subjects in a study of the effectiveness of influenza vaccine

Table 3
Table 3

Effectiveness of influenza vaccination in reducing the risk of hospitalization for pneumonia and influenza or death from all causes

As expected, the absolute benefits of vaccination varied according to subgroup (table 4). Vaccination prevented 3.8 of 1000 healthy persons from being hospitalized for pneumonia/influenza or dying, whereas vaccination prevented 18.0 of 1000 elderly persons with high-risk medical conditions from experiencing one of these complications during year 1. Findings for year 2 were similar, with an absolute risk reduction of 3.5 events per 1000 healthy elderly persons and 8.5 events per 1000 high-risk elderly persons. The numbers needed to treat to prevent 1 outcome also reflected the higher level of absolute benefits experienced by the high-risk subgroups. In year 1, 26–56 persons in the various high-risk subgroups would have had to be vaccinated to prevent 1 outcome, whereas 264 healthy persons would have had to be vaccinated to prevent 1 outcome (table 4). In year 2, the NNTs were 50–150 among persons in the high-risk subgroups and 290 for healthy persons. (table 4)

Table 4
Table 4

Absolute risk reductions for pneumonia/influenza hospitalizations or death due to all causes associated with vaccination and corresponding numbers of persons needed to vaccinate to prevent 1 outcome

Previous SectionNext Section

Discussion

Our study is unique in that the size of the cohorts allowed us to obtain precise estimates of clinical influenza vaccine effectiveness across different high-risk subgroups of elderly persons and to demonstrate the consistency of vaccine effectiveness across the specific risk groups. Our results also demonstrate that rates of hospitalization for pneumonia/influenza or death were highest among unvaccinated persons with high-risk conditions (including heart and lung disease) or immunosuppression, and they were lowest in elderly persons without high-risk medical conditions, which is in accordance with the findings of studies reported elsewhere [3–7, 16]. Thus, the absolute benefits of vaccination were highest among the high-risk elderly people. Nevertheless, vaccination provided benefits in all of the subgroups, including healthy elderly individuals, with reductions in risk for hospitalization or death of 9.8 events per 1000 vaccinated persons in year 1 and 5.9 events per 1000 vaccinated persons in year 2

Studies elsewhere of the benefits of influenza vaccination among elderly persons with chronic lung disease have also shown that there are significant benefits associated with vaccination. Hak et al. [29] found that influenza vaccination of such patients was associated with a 50% reduction in influenza-associated complications, including pneumonia, cardiac disease, or death. Vaccine effectiveness was even higher (80%) among persons who also had preexisting cardiovascular disease. Nichol et al. [30] found that influenza vaccination of elderly persons with chronic lung disease was also highly beneficial. In that study, vaccination was associated with a 52% reduction in the incidence of hospitalizations for pneumonia/influenza and a 70% reduction in deaths. Because recent randomized trials have demonstrated the safety of vaccination among people with asthma [31, 32], our results clearly support a vaccination policy for these patients

Persons in our study with immunosuppression who were vaccinated experienced substantially fewer influenza-associated complications than did their nonvaccinated counterparts. This is in agreement with results of a recent study of seroconversion among patients with lung cancer [33] and a randomized, controlled trial of influenza vaccine effectiveness among HIV-infected persons [34]. In the latter study, vaccine recipients had no influenza infection, whereas 25% of the recipients of saline placebo contracted influenza, for a protective efficacy of 100% (95% CI, 73–100)

People with diabetes are also at higher risk for serious complications due to influenza and benefit from vaccination. Colquhoun et al. [35] performed a case-control study that involved people with diabetes and estimated that influenza vaccination reduced the incidence of hospital admissions for pneumonia/influenza or diabetic events by 79%. US data from the Behavioral Risk Factor Surveillance System show that, although elderly persons with diabetes are more likely to vaccinated than are other elderly persons, >25% still remain unvaccinated [8]. Our findings support additional vaccination efforts for these groups

Govaert et al. [15] randomly allocated 1838 healthy elderly persons to receive either influenza vaccine or placebo. The incidence of clinical influenza infection was 20 and 30 cases per 1000 vaccinees and nonvaccinees, respectively, and the vaccine effectiveness was 47%. The absolute reduction in risk was 10 influenza cases per 1000 vaccinated persons, a finding of unclear clinical meaning, because the outcome included both mild and severe influenza-associated illnesses but did not include influenza-associated complications. However, we have shown that an absolute reduction in serious outcomes of 3.5–3.8 cases per 1000 healthy elderly persons can be attained, which highlights the importance and potential benefits of immunization even for low-risk elderly people

Even during the second year of the study, when there was a poor match between the predominant circulating virus (A/Sydney/H3N2) and the corresponding vaccine strain [25], we demonstrated a significant level of vaccine effectiveness in all of the subgroups we studied, although the level observed was somewhat lower than that seen during the first year of the study. This finding suggests that there was some degree of cross-protection afforded by the vaccine. Varying levels of cross-protection have been observed in other studies conducted during years when there has been a poor vaccine–circulating virus strain match [36]

Several limitations of the present study deserve comment. The use of a nonexperimental study design may have resulted in the potential incomparability of prognosis among vaccinees and nonvaccinees [23]. Confounding may have led to an unequal balance of average risk of outcomes between the comparison groups. We were able to capture data on comorbidity, age, sex, and baseline health care use, and we adjusted for these data in the analyses. Nevertheless, our results should be interpreted with some caution

Misclassification of vaccination status may have occurred in the present study, most likely because of a failure to obtain data about vaccination status. If such a misclassification was substantial, this likely would have biased the study findings to lower vaccine effectiveness rates. However, data were available from 2 managed-care organizations, which suggests that there was probably minimal misclassification of vaccination status. Data from a member survey conducted in 1995 for HP show that >95% of the vaccinated elderly members of the plan reported receiving their influenza vaccinations at a health plan site [37], and the agreement between medical records and the computerized databases is >90% for vaccination status [16]. Likewise, the findings of annual membership surveys conducted from 1990 through 1995 at KPNW indicate that >90% of vaccinated elderly plan members received their vaccine at a health plan site. Furthermore, chart audits from the plan indicate that >98% of influenza vaccinations are recorded in the organization's computerized database (J. Mullooly, personal communication)

We did not include other outcomes associated with influenza infections, such as acute respiratory or cardiac disease or diabetes events leading to clinic visits or hospitalizations [2, 4, 7, 16]. We limited our analysis to the serious influenza-associated outcomes of hospitalization for pneumonia/influenza and all-cause death, because the attributable fraction due to influenza infections is relatively high during influenza seasons [1]. However, the overall absolute health benefits of vaccination might have been underestimated [4, 7, 16]

We lacked information on pneumococcal vaccination status. In a recent cohort study that involved elderly persons with chronic pulmonary disease, two-thirds of patients had received vaccine [38]. Results revealed that reductions associated with pneumococcal vaccination were additive to those of influenza vaccination. However, it is unclear how this might have affected the estimates for the effectiveness in other subgroups [39]

Our study included information only for persons aged ⩾65 years. Recently, recommendations in the United States for annual influenza vaccination were modified to include all persons aged 50–64 years as a second-tier priority group, because these persons are likely to have underlying medical conditions that place them at higher risk for complications due to influenza [40]. How our study results might apply to this segment of the population is unclear

It often takes an enormous effort to increase influenza vaccination coverage in a large-scale prevention program, despite the fact that the vaccine is inexpensive, well tolerated, and effective. Health policy makers, physicians, and patients need valid and precise information to justify the ongoing support of such strategies. This type of evidence is also helpful in identifying the highest-priority groups for vaccination when there is a delay or shortage of vaccine supplies, as was the case in the United States during the 2000–2001 season [20, 21]. In the case of an influenza pandemic, a substantial shortfall of vaccine will likely occur as well, and such information will undoubtedly be of use in that event

The elderly population is at increased risk of developing serious complications associated with influenza. Our data support current recommendations in the United States and other developed countries for the vaccination of all persons aged ⩾65 years [40, 41]. Both healthy and high-risk elderly people derive substantial benefits from vaccination, and age-based strategies have been more effective than risk condition–based vaccination strategies in achieving high vaccination rates [42]. However, our findings also highlight the fact that elderly people with underlying medical conditions do have significantly higher rates of hospitalization and death, and, therefore, the absolute reduction in outcomes per 1000 vaccinated persons is higher in these groups. Thus, although all persons aged ⩾65 years benefit from vaccination and should be targeted for annual vaccination, efforts should be renewed, especially to ensure vaccination among persons with cardiopulmonary disease, diabetes, cancer, transplants, immunodeficiency, and other high-risk conditions

Previous SectionNext Section

Footnotes

  • Financial support: This project was funded and sponsored by the National Vaccine Program Office and the Centers for Disease Control and Prevention through an agreement with the American Association of Health Plans. E.H.'s participation was supported by a grant from the Dutch Asthma Foundation, Leusden, The Netherlands

  • Received December 12, 2001.
  • Revision received February 11, 2002.
Previous Section
 

References

  1. ↵
    1. Simonsen L,
    2. Clarke MJ,
    3. Williamson GD,
    4. et al
    . The impact of influenza epidemics on mortality: introducing a severity index. Am J Public Health 1997;87:1944-50.
    MedlineWeb of Science
  2. ↵
    1. McBean AM,
    2. Babish JD,
    3. Warren JL
    . The impact and cost of influenza in the elderly. Arch Intern Med 1993;153:2105-11.
    Abstract/FREE Full Text
  3. ↵
    1. Ahmed AH,
    2. Nicholson KG,
    3. Nguyen-Van-Tam JS
    . Reduction in mortality associated with influenza vaccine during 1989–;90 epidemic. Lancet 1995;346:591-5.
    CrossRefMedlineWeb of Science
  4. ↵
    1. Fedson DS,
    2. Wadja A,
    3. Nicol JP
    . Clinical effectiveness of influenza vaccination in Manitoba. JAMA 1993;270:1956-61.
    Abstract/FREE Full Text
    1. Ohmit SE,
    2. Monto AS
    . Influenza vaccine effectiveness in preventing hospitalization for pneumonia among the elderly during influenza A and type B seasons. Int J Epidemiol 1995;24:1240-8.
    Abstract/FREE Full Text
  6. ↵
    1. Flemming DM,
    2. Watson JM,
    3. Nicholas S
    . Study on the effectiveness of influenza vaccination in the elderly in the epidemic of 1989–;90 using a general practice database. Epidemiol Infect 1995;115:581-9.
    Medline
  7. ↵
    1. Nichol KL,
    2. Margolis KL,
    3. Wuorenma J,
    4. et al
    . The efficacy and cost-effectiveness of vaccination against influenza among elderly persons in the community. N Engl J Med 1994;331:778-84.
    CrossRefMedlineWeb of Science
  8. ↵
    1. Centers for Disease Control and Prevention
    . Influenza and pneumococcal vaccination levels among persons aged 65 years—United States, 1999. MMWR Morb Mortal Wkly Rep 2001;50:532-7.
    Medline
  9. ↵
    1. Ambrosch F,
    2. Fedson DS
    . Influenza vaccination in 29 countries: an update to 1997. Pharmacoeconomics 1999;16(Suppl 1):47-54.
    CrossRefMedlineWeb of Science
  10. ↵
    1. Centers for Disease Control and Prevention
    . Reasons reported by Medicare beneficiaries for not receiving influenza and pneumococal vaccinations—United States, 1996. MMWR Morb Mortal Wkly Rep 1999;48:886-90.
    Medline
    1. Nichol KL,
    2. MacDonald R,
    3. Hauge M
    . Factors associated with influenza and pneumococcal vaccination behavior among high-risk adults. J Gen Intern Med 1996;11:673-7.
    MedlineWeb of Science
  12. ↵
    1. Centers for Disease Control and Prevention
    . Adult immunization: knowledge, attitudes and practices—DeKalb and Fulton counties, Georgia, 1988. MMWR Morb Mortal Wkly Rep 1988;37:657-61.
    Medline
  13. ↵
    1. Glezen WP,
    2. Decker M,
    3. Perrotta DM
    . Survey of underlying conditions of persons hospitalized with acute respiratory disease during influenza epidemics in Houston, 1978–;81. Am Rev Respir Dis 1987;136:550-5.
    MedlineWeb of Science
  14. ↵
    1. Paul WS,
    2. Cowan J,
    3. Jackson GG
    . Acute respiratory illness among immunized and non-immunized patients with high-risk factors during a split season of influenza A and B. J Infect Dis 1988;157:633-9.
    Abstract/FREE Full Text
  15. ↵
    1. Govaert ThME,
    2. Thijs CTMCN,
    3. Masurel N,
    4. Sprenger MJW,
    5. Dinant GJ,
    6. Knottnerus JA
    . The efficacy of influenza vaccination in elderly individuals: a randomized double-blind placebo-controlled trial. JAMA 1994;272:1661-5.
    Abstract/FREE Full Text
  16. ↵
    1. Nichol KL,
    2. Wuorenma J,
    3. VonSternberg T
    . Benefits of influenza vaccination for low-, intermediate- and high-risk senior citizens. Arch Intern Med 1998;158:1769-76.
    Abstract/FREE Full Text
  17. ↵
    1. Mullooly JP,
    2. Bennett MD,
    3. Hornbrook MC,
    4. et al
    . Influenza vaccination of elderly persons: cost-effectiveness in a health maintenance organization. Ann Intern Med 1994;121:947-52.
    Abstract/FREE Full Text
  18. ↵
    1. Barker WH,
    2. Mullooly JP
    . Influenza vaccination of elderly persons: reduction in pneumonia and influenza hospitalizations and deaths. JAMA 1980;244:2547-9.
    Abstract/FREE Full Text
  19. ↵
    1. Nicholson KG,
    2. Snacken R,
    3. Palache AM
    . Influenza immunization policies in Europe and the United States. Vaccine 1995;13:365-9.
    CrossRefMedlineWeb of Science
  20. ↵
    1. Centers for Disease Control and Prevention
    . Notice to readers: delayed supply of influenza vaccine and adjunct ACIP influenza vaccine recommendations for the 2000–;01 influenza season. MMWR Morb Mortal Wkly Rep 2000;49:619-22.
    Medline
  21. ↵
    1. Centers for Disease Control and Prevention
    . Notice to readers: updated recommendations from the Advisory Committee on Immunization Practices in response to delays in supply of influenza vaccine for the 2000–;01 season. MMWR Morb Mortal Wkly Rep 2000;49:888-92.
    Medline
  22. ↵
    1. Nordin J,
    2. Mullooly J,
    3. Poblete S,
    4. et al
    . Influenza vaccine effectiveness in preventing hospitalizations and deaths in persons 65 years or older in Minnesota, New York, and Oregon: data from 3 health plans. J Infect Dis 2001;184:665-70.
    Abstract/FREE Full Text
  23. ↵
    1. Grobbee DE,
    2. Hoes AW
    . Confounding and indication for treatment in evaluation of drug treatment for hypertension. BMJ 1997;315:1151-4.
    FREE Full Text
  24. ↵
    1. Centers for Disease Control and Prevention
    . Update: influenza activity—United States and worldwide, 1996–;97 season, and composition of the 1997–;98 influenza vaccine. MMWR Morb Mortal Wkly Rep 1997;46:325-30.
    Medline
  25. ↵
    1. Centers for Disease Control and Prevention
    . Update: influenza activity—United States and worldwide, 1996–;97 season, and composition of the 1998–;99 influenza vaccine. MMWR Morb Mortal Wkly Rep 1998;47:280-4.
    Medline
  26. ↵
    1. Simonsen L,
    2. Fukuda K,
    3. Schonberger LB,
    4. Cox NJ
    . The impact of influenza epidemics on hospitalizations. J Infect Dis 2000;181:831-7.
    Abstract/FREE Full Text
  27. ↵
    1. Neuzil KM,
    2. Reed GW,
    3. Mitchel EF,
    4. Griffin MR
    . Influenza-associated morbidity and mortality in young and middle-aged women. JAMA 1999;281:901-7.
    Abstract/FREE Full Text
  28. ↵
    1. Cook DJ,
    2. Sackett DL
    . The number needed to treat: a clinically useful measure of treatment effect. BMJ 1995;310:452-4.
    FREE Full Text
  29. ↵
    1. Hak E,
    2. van Essen GA,
    3. Buskens E,
    4. et al
    . Is immunising all patients with chronic lung disease in the community against influenza cost-effective? Evidence from a general practice based clinical prospective cohort study in Utrecht, the Netherlands. J Epidemiol Community Health 1998;52:120-5.
    Abstract
  30. ↵
    1. Nichol KL,
    2. Baken L,
    3. Nelson A
    . Relation between influenza vaccination and outpatient visits, hospitalizations, and mortality in elderly persons with chronic lung disease. Ann Intern Med 1999;130:397-403.
    Abstract/FREE Full Text
  31. ↵
    1. Nicholson KG,
    2. Nguyen-Van-Tam JS,
    3. Ahmed AH,
    4. et al
    . Randomised placebo-controlled crossover trial on effects of inactivated influenza vaccine on pulmonary function in asthma. Lancet 1998;351:326-31.
    CrossRefMedlineWeb of Science
  32. ↵
    1. American Lung Association Asthma Clinical Research Centers
    . The safety of inactivated influenza vaccine in adults and children with asthma. N Engl J Med 2001;345:1529-36.
    CrossRefMedlineWeb of Science
  33. ↵
    1. Anderson H,
    2. Petrie K,
    3. Berrisford C,
    4. Charlett A,
    5. Thatcher N,
    6. Zambon M
    . Seroconversion after influenza vaccination in patients with lung cancer. Br J Cancer 1999;80:219-20.
    CrossRefMedlineWeb of Science
  34. ↵
    1. Tasker SA,
    2. Treanor JJ,
    3. Paxton WB,
    4. Wallace MR
    . Efficacy of influenza vaccination in HIV-infected persons: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999;131:430-3.
    Abstract/FREE Full Text
  35. ↵
    1. Colquhoun AJ,
    2. Nicholson KG,
    3. Botha JL,
    4. Raymond NT
    . Effectiveness of influenza vaccine in reducing hospital admissions in people with diabetes. Epidemiol Infect 1997;119:335-41.
    CrossRefMedline
  36. ↵
    1. Brown LE,
    2. Hampson AW,
    3. Webster RG
    1. Couch RB,
    2. Keitel WA,
    3. Cate TR,
    4. et al.
    ; Brown LE, Hampson AW, Webster RG, editors. Prevention of influenza virus infections by current inactivated influenza virus vaccines. Options for the control of influenza, III Amsterdam: Elsevier Science BV; 1996:97-106.
  37. ↵
    1. MacDonald R,
    2. Baken L,
    3. Nelson A,
    4. Nichol KL
    . Validation of self-report of influenza and pneumococcal vaccination status in elderly outpatients. Am J Prev Med 1999;16:173-7.
    CrossRefMedlineWeb of Science
  38. ↵
    1. Nichol KL,
    2. Baken L,
    3. Wuorenma J,
    4. Nelson A
    . The health and economic benefits associated with pneumococcal vaccination of elderly persons with chronic lung disease. Arch Intern Med 1999;159:2437-42.
    Abstract/FREE Full Text
  39. ↵
    1. Hak E,
    2. Van Essen GA,
    3. Grobbee DE,
    4. Verheij TJM
    . Effectiveness of pneumococcal vaccine [letter]. Lancet 1998;351:1283.
    MedlineWeb of Science
  40. ↵
    1. Bridges CB,
    2. Fukuda K,
    3. Cox NJ,
    4. Singleton JA
    . Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2001;50(RR-4):1-44.
    Medline
  41. ↵
    1. Ambrosch F,
    2. Fedson DS
    . Influenza vaccination in 29 countries: an update to 1997. Pharmacoeconomics 1999;16(Suppl 1):47-54.
    CrossRefMedlineWeb of Science
  42. ↵
    1. Honkanen PO,
    2. Keistinen T,
    3. Kivela SL
    . The impact of vaccination strategy and methods of information on influenza and pneumococcal vaccination coverage in the elderly population. Vaccine 1997;15:317-20.
    CrossRefMedlineWeb of Science
| Table of Contents

This Article

  1. Clin Infect Dis. (2002) 35 (4): 370-377. doi: 10.1086/341403
  1. AbstractFree
  2. » Full Text (HTML)Free
  3. Full Text (PDF)Free

Classifications

Share

  1. Email this article

Navigate This Article

Current Issue

  1. March 1, 2012 54 (5)
  1. Clinical Infectious Diseases
  1. Alert me to new issues

Most