Vaccine 31 (2013) 718–724

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Vaccine
journal homepage: www.elsevier.com/locate/vaccine

Effectiveness of influenza vaccination in elderly diabetic patients: A retrospective

cohort study
I-Kuan Wang a,b,c , Cheng-Li Lin d,e , Yi-Chih Chang f , Po-Chang Lin g , Chih-Chia Liang a , Yao-Lung Liu a ,
Chiz-Tzung Chang a , Tzung-Hai Yen h , Chiu-Ching Huang a , Fung-Chang Sung d,e,∗
a
Division of Kidney Disease, China Medical University Hospital, Taichung, Taiwan
b
Department of Internal Medicine, China Medical University College of Medicine, Taichung, Taiwan
c
Institute of Clinical Medical Science, China Medical University College of Medicine, Taichung, Taiwan
d
Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan
e
Department of Public Health, China Medical University, Taichung, Taiwan
f
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan
g
Division of Infection, China Medical University Hospital, Taichung, Taiwan
h
Division of Nephrology, Chang Gung Memorial Hospital, Taipei, Chang Gung University College of Medicine, Taipei, Taiwan

a r t i c l e i n f o a b s t r a c t

Article history: Purpose: Studies regarding the clinical benefits of influenza vaccination in diabetic patients are limited.
Received 3 September 2012 This study evaluated if the elderly diabetic patients who have had influenza vaccination would have
Received in revised form 22 October 2012 benefits such as reduced medical care and mortality.
Accepted 2 November 2012
Methods: We used the universal insurance claims data from 2001 to 2009 in Taiwan to identify annual
Available online 12 November 2012
elderly patients with diabetes cohorts with (N = 4454) and without (N = 4571) influenza vaccination.
The risk of developing pneumonia or influenza, respiratory failure, intensive care, hospitalization, and
Keywords:
mortality were measured and compared between cohorts within one year of follow-up.
Vaccine
Diabetes
Results: The vaccine cohort had lower incidences of pneumonia or influenza and respiratory failure com-
Hospitalization pared with the non-vaccine cohort. More importantly, the vaccine cohort had a hospitalization rate that
Influenza was 11% less than the non-vaccine cohort (29.6 vs. 33.1 per 100 person-years) with an adjusted hazard
Mortality ratio (HR) of 0.88 (95% CI 0.81–0.96). The vaccine cohort was also less likely to be admitted to the intensive
care unit (ICU) [0.58 vs. 2.05 per 100 person-year; adjusted HR 0.30 (95% CI 0.19–0.47)] and less likely
to expire [3.13 vs. 7.96 per 100 person-year; adjusted HR 0.44 (95% CI 0.36–0.54)]. Influenza vaccination
reduced the hospitalization cost by 1282.6 USD, compared with patients without influenza vaccination
(95% CI −2210.3, −354.8).
Conclusion: Influenza vaccination is associated with a reduced risk of morbidity, hospitalization, ICU
admissions, and mortality. In addition, the hospitalization cost is reduced.
Crown Copyright © 2012 Published by Elsevier Ltd. All rights reserved.

1. Introduction problem worldwide. A total of 439 million adults are estimated

The influenza virus, which is a common transmissible human
respiratory virus, is a major cause of illness and death. In the
Unites States, influenza resulted in more than 225,000 hospi-
talizations and 36,000 deaths annually [1,2]. The morbidity and
mortality of influenza is high among the elderly, pregnant women,
immunocompromised hosts, and those with chronic diseases such
as diabetes mellitus (DM) [3]. DM is a serious and growing health
∗ Corresponding author at: China Medical University College of Public Health, 91
Hsueh Shih Road, Taichung 404, Taiwan. Tel.: +886 4 2206 2295;
fax: +886 4 2201 9901.
E-mail addresses: ikwang@mail.cmuh.org.tw, ikwang@mail.cmu.edu.tw
(F.-C. Sung).
to be affected with DM by 2030 with a 20% increase in developed
countries and 69% increase in developing countries from 2010 to
2030 [4]. Abnormal glucose metabolism has been associated with
the dysfunction of leukocytes, such as phagocytosis, chemotaxis,
and leukocyte adherence [5]. Therefore, diabetic patients have a
high morbidity and mortality from infection [6]. These patients
are susceptible to influenza and pneumonia [7,8]. In addition, dia-
betic patients were reported to be two to four times more likely to
die from influenza and pneumonia compared with people without
diabetes [9].
Due to ethical considerations, performing randomized con-
trolled trials for influenza vaccination is difficult. Observation
studies have found that influenza vaccination can reduce the risk
of hospitalizations and deaths in elderly and high-risk individ-
uals [10,11]. However, studies on the clinical benefits of such a

0264-410X/$ – see front matter. Crown Copyright © 2012 Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.vaccine.2012.11.017
 I.-K. Wang et al. / Vaccine 31 (2013) 718–724 719

vaccination for DM patients are limited [11–14]. The aim of this Table 1
Baseline demographic status and comorbidity in diabetic patients with and without
study is to evaluate the efficacy of influenza vaccination in reducing
influenza vaccination.
morbidity and mortality in newly diagnosed elderly DM patients
using a population-based cohort study. Influenza vaccine P value

No (N = 4454) Yes (N = 4571)

2. Methods Age, mean ± SD 73.2 ± 6.79 73.1 ± 5.87 0.17

Stratified age
2.1. Data sources 65–74 2856(64.1) 3098(67.8) 0.0003a
75+ 1598(35.9) 1473(32.2)
This study used a subset of claims data from the National
Gender
Health Research Institutes Database (NHID) obtained from Taiwan’s Women 2250(50.5) 2287(50.0) 0.65
National Health Insurance program. The National Health Insurance Men 2204(49.5) 2284(50.0)
system in Taiwan is a universal insurance program established by Comorbidity
the Bureau of National Health Insurance. The insurance program CAD 1340(30.1) 1566(34.3) <0.0001a
started in March 1995 and has now covered approximately 99% of CHF 907(20.4) 1035(22.6) 0.008a
the 23.74 million residents in Taiwan [15]. This subset data included Hypertension 3234(72.6) 3707(81.1) <0.0001a
Hyperlipidemia 1526(34.3) 2097(45.9) <0.0001a
claims data from 2001 to 2009 that were randomly sampled in one
Atrial fibrillation 150(3.37) 179(3.92) 0.16
million insured people from the whole population. The data are COPD 1584(35.6) 1713(37.5) 0.06
composed of comprehensive information on basic patient demo- Renal disease 623(14.0) 691(15.1) 0.13
graphic data, dates of clinical visits, diagnostic codes, details of Cancer 1375(30.9) 1448(31.7) 0.41
prescriptions, expenditure amounts, and other data as previously Chronic hepatitis 1671(37.5) 1856(40.6) 0.003a
Stroke 1297(29.1) 1424(31.2) 0.04a
detailed. Patient identification numbers were scrambled to pro- Dementia 254(5.70) 271(5.93) 0.65
tect patient privacy. The International Classification of Disease, 9th Rehabilitation 525(11.8) 667(14.6) <0.0001a
Revision, Clinical Modification (ICD-9-CM) was used to identify the
Abbreviations: SD, standard deviation; CAD, coronary artery disease; CHF, congestive
diagnosis of diseases. This study was approved by the Institutional heart failure; COPD, chronic obstructive pulmonary disease.
Review Board of China Medical University. a
Chi-square test.

2.2. Study subjects hypertension, hyperlipidemia, atrial fibrillation, chronic obstruc-

From the claims data of 2001–2009, the elderly (age  65 years)
with newly diagnosed diabetes (ICD-9-CM code 250) were iden-
tified annually from 2001 to 2009. Among patients with DM, we
further identified annually those who had completed the seasonal
influenza vaccination (ICD-9-CM code V04.7 and V04.8) and con-
sidered them as the vaccine cohort with the vaccination date as the
index date. The non-vaccine cohort was randomly selected annu-
ally from the remaining patients without influenza vaccinations.
For each patient in the vaccine cohort, one comparison subject was
selected with frequency matched by sex and the index date. Each
subject in both cohorts was followed up for one year, starting on
the date being selected into the cohort. We excluded persons with
prior hospitalizations (N = 254) and those who received pneumo-
coccal vaccine (N = 329). About 4571 participants were selected as
the vaccine cohort, and 4454 participants were selected as the non-
vaccine cohort. The circulation of influenza virus had been reported
during the study period [16–18].
2.3. Outcome measures
The follow-up person-year was measured for each patient from
the index date for 365 days or until censored because of death
or withdrawal from the insurance system in the follow-up year.
We were interested in the outcome events of total hospitaliza-
tion, pneumonia or influenza, respiratory failure, or intensive care
unit (ICU) admission or death. The comorbidities included coronary
artery disease (CAD), congestive heart failure (CHF), hypertension,
hyperlipidemia, atrial fibrillation, chronic obstructive pulmonary
disease (COPD), renal disease, cancer, chronic hepatitis, stroke, and
dementia (the Appendix lists ICD codes). Rehabilitation was iden-
tified according to the procedures codes in the claims data.
2.4. Statistical analysis
The distributions of demographic status and comorbidities
including age, sex, coronary artery disease, congestive heart failure,
tive pulmonary disease, renal disease, cancer, chronic hepatitis,
stroke, dementia, and rehabilitation were compared between the
vaccine and the non-vaccine cohorts. The differences were exam-
ined using the 2 test for categorical variables and the t-test for
continuous variables. The follow-up time was used to estimate
the age-specific incidence rates of hospitalization, pneumonia or
influenza, respiratory failure, ICU admission, and mortality. We
measured rates of hospitalization and mortality by the comor-
bidity status. Poisson regression was used to estimate incidence
rate ratio (IRR) of the vaccine cohort to the non-vaccine cohort
with a 95% confidence interval (CI). The Cox proportional hazards
regression model was used to estimate the corresponding hazard
ratios (HRs) and 95% CIs. Age-specific rates (65–74, and 75 and
above years) and the vaccine cohort to the non-vaccine cohort rate
ratios for hospitalization, pneumonia or influenza, respiratory fail-
ure, ICU admission, and mortality were measured. Multivariable
regression analysis was used to estimate the cost of hospitaliza-
tion associated with influenza vaccination. The variables including
sex, age, and comorbidities were selected in a stepwise manner.
We used the Kaplan–Meier method to compare the probability of
hospitalization-free events and survival between the two cohorts.
We used the log-rank test to examine the differences. SAS version
9.1 (SAS Institute, Cary, NC, USA) was used for data analyses. P < 0.05
was considered statistically significant.
3. Results
In Taiwan, the prevalence of diabetes patients in the elderly
increased from 19.4% in 2001 to a peak of 24.6% in 2009 (data
not shown). The study subjects were composed of 4571 newly
diagnosed diabetic patients with influenza vaccination in the vac-
cine cohort and 4454 newly diagnosed diabetic patients without
influenza vaccination in the non-vaccine cohort. The mean ages
of the two cohorts were not statistically different, but the vaccine
cohort had lesser subjects aged 75 years, 32.2% vs. 35.9% (Table 1).
Compared with the non-vaccine cohort, the patients in the vaccine
cohort were more prevalent with comorbidities. The vaccine cohort
720 I.-K. Wang et al. / Vaccine 31 (2013) 718–724

Table 2
Hospitalization risk between DM patients with and without influenza vaccination among comorbidities.

Outcome Non-vaccine Vaccine IRRb (95% CI) Adjusted HRc (95% CI)
a a
Event PY Rate Event PY Rate

Hospitalization
CAD
No 741 2515 29.5 616 2524 24.4 0.83(0.74, 0.93)** 0.84(0.75, 0.93)**
Yes 423 1007 42.0 491 1222 40.2 0.96(0.82, 1.12) 0.97(0.85, 1.10)

CHF
No 835 2857 29.2 764 2934 26.0 0.89(0.80, 0.99)* 0.89(0.81, 0.99)*
Yes 329 665 49.5 343 811 42.3 0.85(0.71, 1.03) 0.89(0.76, 1.03)

Hypertension
No 258 1011 25.5 171 732 23.4 0.92(0.74, 1.13) 0.92(0.76, 1.12)
Yes 906 2511 36.1 936 3014 31.1 0.86(0.77, 0.96)** 0.88(0.80, 0.96)**

Hyperlipidemia
No 839 2262 37.1 677 1986 34.1 0.92(0.82, 1.04) 0.88(0.80, 0.97)*
Yes 325 1260 25.8 430 1759 24.5 0.95(0.81, 1.11) 0.91(0.78, 1.05)

Atrial fibrillation
No 1095 3426 32.0 1036 3612 28.7 0.90(0.82, 0.99)* 0.90(0.83, 0.98)*
Yes 69 96 71.9 71 133 53.4 0.74(0.48, 1.13) 0.74(0.53, 1.04)

COPD
No 613 2359 26.0 571 2402 23.8 0.91(0.81, 1.03) 0.91(0.81, 1.02)
Yes 551 1163 47.4 536 1343 39.9 0.84(0.73, 0.97)* 0.87(0.77, 0.98)*

Renal disease
No 946 3064 30.9 882 3208 27.5 0.89(0.80, 0.99)* 0.89(0.81, 0.98)*
Yes 218 457 47.7 225 537 41.9 0.88(0.70, 1.11) 0.89(0.73, 1.07)

Cancer
No 730 2508 29.1 721 2606 27.7 0.95(0.85, 1.07) 0.93(0.84, 1.03)
Yes 434 1014 42.8 386 1140 33.9 0.79(0.67, 0.93)** 0.81(0.71, 0.93)**

Chronic hepatitis
No 719 2208 32.6 638 2246 28.4 0.87(0.77, 0.98)* 0.87(0.78, 0.97)*
Yes 445 1314 33.9 469 1499 31.3 0.92(0.80, 1.07) 0.92(0.81, 1.05)

Stroke
No 682 2589 26.3 636 2645 24.1 0.91(0.81, 1.03) 0.90(0.81, 1.01)
Yes 482 933 51.7 471 1100 42.8 0.83(0.71, 0.97)* 0.87(0.76, 0.98)*

Dementia
No 1034 3367 30.7 978 3560 27.5 0.89(0.81, 0.99)* 0.89(0.82, 0.98)*
Yes 130 155 83.9 129 185 69.7 0.83(0.60, 1.15) 0.81(0.64, 1.04)

Rehabilitation
No 986 3134 31.5 910 3212 28.3 0.90(0.81, 1.00)* 0.90(0.83, 0.99)*
Yes 178 388 45.9 197 533 37.0 0.80(0.63, 1.03) 0.80(0.65, 0.98)*
a
Rate, incidence rate, per 100 person-year.
b
IRR, incidence rate ratio.
c
Adjusted HR: adjusted for age, sex, and co-morbidities.
*
p < 0.05.
**
p < 0.01.

had significant differences in proportions of CAD, CHF, hyperten-
sion, hyperlipidemia, and chronic hepatitis.
Table 2 presents rates of hospitalization by comorbidity for both
cohorts and IRR of the vaccine cohort to the non-vaccine cohort
and adjusted HR of hospitalization. The hospitalization risks were
consistently lower in the vaccine cohort than in the non-vaccine
cohort. The IRR associated with cancer (0.79; 95% CI 0.67–0.93) was
the lowest among all comorbidities, with an adjusted HR of 0.81
(95% CI 0.71–0.93).
Table 3 shows a pattern in mortality similar to that in hospi-
talization. The effect of vaccination was much greater in reducing
deaths than in reducing hospitalization. Regardless the comorbid-
ity status, all IRRs of the vaccine cohort to the non-vaccine cohort
were significantly reduced to 0.50 or less with low HRs as well.
The overall hospitalization incidence rate was 11% lower in the
vaccine cohort than in the non-vaccine cohort (29.6 vs. 33.1 per
100 person-year incidence, IRR = 0.89, 95% CI = 0.81–0.98) with an
adjusted HR of 0.88 (95% CI = 0.81–0.96) (Table 4). The incidence
rates of pneumonia or influenza and respiratory failure were also
lower in the vaccine cohort than in the non-vaccine cohort. The
adjusted HRs also demonstrated the protective effects from the
vaccination. Compared with the patients in the non-vaccine cohort,
those in the vaccine cohort were less likely to be admitted to the
ICU [0.58 vs. 2.05 person-year; adjusted HR 0.30 (95% CI 0.19–0.47)]
and expire [3.13 vs. 7.96 person-year; adjusted HR 0.44 (95% CI
0.36–0.54)]. The age-specific analysis showed that the vaccine to
non-vaccine cohort rate ratios of hospitalization, pneumonia or
influenza, respiratory failure, and ICU admission were lower for
the older age group.
Fig. 1A–D shows that the vaccine cohort had a significantly
lower cumulative proportion of hospitalization (P = 0.01) (Fig. 1A),
pneumonia or influenza (P = 0.03) (Fig. 1B), respiratory failure
(P = 0.0002) (Fig. 1C), ICU admission (P < 0.0001) (Fig. 1D), and mor-
tality (P < 0.0001) (Fig. 1E) compared with the non-vaccine cohort.
Table 5 shows the stepwise regression analysis in evaluating the
factors associated with hospitalization cost. Compared with DM
patients without influenza vaccination, hospitalization cost was
1282.6 USD less for DM patients with influenza vaccination. Male,
 I.-K. Wang et al. / Vaccine 31 (2013) 718–724 721

Fig. 1. Probability free of hospitalization (A), pneumonia or influenza (B), respiratory failure (C), intensive care unit admission (D), and mortality (E) for diabetic patients
with (dashed line) or without (solid line) influenza vaccination.
722 I.-K. Wang et al. / Vaccine 31 (2013) 718–724

Table 3
Mortality risk between DM patients with and without influenza vaccination among comorbidities.

Outcome Non-vaccine Vaccine IRRb (95% CI) Adjusted HRc (95% CI)
a a
Event PY Rate Event PY Rate

Mortality
CAD
No 217 2857 7.60 89 2816 3.16 0.42(0.36, 0.49)** 0.47(0.37, 0.60)**
Yes 108 1228 8.79 45 1472 3.06 0.35(0.28, 0.43)** 0.39(0.27, 0.55)**

CHF
No 238 3253 7.32 104 3300 3.15 0.43(0.37, 0.50)** 0.47(0.37, 0.59)**
Yes 87 832 10.5 30 987 3.04 0.29(0.22, 0.38)** 0.36(0.24, 0.55)**

Hypertension
No 72 1125 6.40 26 810 3.21 0.50(0.38, 0.67)** 0.55(0.35, 0.86)**
Yes 253 2960 8.55 108 3478 3.11 0.36(0.31, 0.42)** 0.42(0.33, 0.52)**

Hyperlipidemia
No 262 2664 9.83 108 2312 4.67 0.48(0.40, 0.56)** 0.49(0.39, 0.61)**
Yes 63 1421 4.43 26 1976 1.32 0.30(0.24, 0.37)** 0.29(0.18, 0.46)**

Atrial fibrillation
No 303 3953 7.67 129 4121 3.13 0.41(0.36, 0.47)** 0.46(0.37, 0.56)**
Yes 22 132 16.7 5 167 2.99 0.18(0.09, 0.36)** 0.19(0.07, 0.50)**

COPD
No 168 2652 6.33 73 2681 2.72 0.43(0.36, 0.51)** 0.49(0.37, 0.65)**
Yes 157 1433 11.0 61 1607 3.80 0.35(0.28, 0.43)** 0.38(0.28, 0.52)**

Renal disease
No 264 3515 7.51 105 3640 2.88 0.38(0.33, 0.44)** 0.42(0.34, 0.53)**
Yes 61 570 10.7 29 648 4.48 0.42(0.30, 0.57)** 0.49(0.31, 0.76)**

Cancer
No 195 2859 6.82 87 2958 2.94 0.43(0.37, 0.50)** 0.49(0.38, 0.63)**
Yes 130 1226 10.6 47 1330 3.53 0.33(0.27, 0.42)** 0.36(0.26, 0.50)**

Chronic hepatitis
No 208 2551 8.15 75 2563 2.93 0.36(0.30, 0.43)** 0.40(0.31, 0.53)**
Yes 117 1534 7.63 59 1725 3.42 0.45(0.37, 0.55)** 0.50(0.36, 0.68)**

Stroke
No 184 2922 6.30 72 2955 2.44 0.39(0.33, 0.45)** 0.42(0.32, 0.55)**
Yes 141 1163 12.1 62 1333 4.65 0.38(0.31, 0.48)** 0.44(0.33, 0.60)**

Dementia
No 271 3870 7.00 109 4042 2.7 0.39(0.34, 0.44)** 0.43(0.35, 0.54)**
Yes 54 215 25.1 25 246 10.2 0.40(0.26, 0.63)** 0.45(0.28, 0.74)**

Rehabilitation
No 279 3607 7.73 113 3656 3.09 0.40(0.35, 0.46)** 0.45(0.36, 0.56)**
Yes 46 478 9.62 21 632 3.32 0.35(0.25, 0.48)** 0.39(0.23, 0.65)**
a
Rate, incidence rate, per 100 person-year.
b
IRR, incidence rate ratio.
c
Adjusted HR: adjusted for age, sex, and co-morbidities.
**
p < 0.01.

comorbidities of COPD, stroke, atrial fibrillation, renal disease,
dementia, and congestive heart failure were positive predictors of
hospitalization cost (Table 5).
4. Discussion
Influenza vaccination for elderly patients that are newly diag-
nosed with DM was associated with lower subsequent morbidities
even when they had been more prevalent with co-morbidities at
the baseline. In addition, influenza vaccination was associated with
a lower all-cause mortality risk of 56%. The hospitalization rate
was reduced for 11% with lower hospitalization cost and shortened
hospitalization length (data not shown). Our further analysis also
revealed that the other health care costs such as ICU costs (data
not shown), were lower in the vaccine cohort compared with the
non-vaccine cohort.
Colquhoun et al. reported a 79% reduction in hospitalizations
of DM patients with the influenza vaccination in all age groups
[12]. However, this reduction is limited to a small number of
patients. Hak et al. found a 50% and 21% significant reduction in
hospitalizations for pneumonia and influenza or death in elderly
DM patients in seasons where the predominant circulating virus
matched well and poorly with the vaccine, respectively [11]. A
study from den Akker et al. found that influenza vaccination was
associated with a significant reductions of 54% and 58% in hospital-
izations and in deaths among adult and elderly DM patients [14]. In
addition, no difference was observed in the vaccine effectiveness
between first-time and repeat vaccinations. Most of these afore-
mentioned studies used the case–control design [12,14]. Moreover,
these studies were based on prevalent DM patients. The duration
of DM may have a confounding effect on the outcome. In addition,
these studies did not consider the confounding effect of pneumo-
coccal vaccination [19]. Therefore, the present study investigated
the effectiveness of influenza vaccination in newly diagnosed DM
patients and excluded the effect of pneumococcal vaccination using
the cohort-study design.
 I.-K. Wang et al. / Vaccine 31 (2013) 718–724 723

Table 4
Hospitalization, pneumonia or influenza, intensive care unit utilization, and mortality by age compared between DM patients with and without influenza vaccination.

Outcome Non-vaccine Vaccine IRRb (95% CI) Adjusted HRc (95% CI)
a a
Event PY Rate Event PY Rate

Hospitalizationc 1164 3522 33.1 1107 3745 29.6 0.89(0.81, 0.98)* 0.88(0.81, 0.96)**
65–74 601 2370 25.4 636 2601 24.5 0.96(0.86, 1.09) 0.91(0.81, 1.02)
75+ 563 1152 48.9 471 1144 41.2 0.84(0.72, 0.98)* 0.85(0.75, 0.96)*

For pneumonia/influenzac 615 3774 16.3 568 3975 14.3 0.88(0.79, 0.98)* 0.86(0.77, 0.97)*
65–74 328 2494 13.2 350 2714 12.9 0.98(0.86, 1.12) 0.93(0.80, 1.09)
75+ 287 1281 22.4 218 1262 17.3 0.77(0.65, 0.92)** 0.78(0.65, 0.93)*

For respiratory failurec 152 4048 3.75 99 4264 2.32 0.62(0.54, 0.70)** 0.67(0.52, 0.86)**
65–74 41 2663 1.54 44 2904 1.52 0.98(0.83, 1.16) 0.97(0.63, 1.49)
75+ 111 1385 8.01 55 1360 4.04 0.50(0.41, 0.62)** 0.55(0.40, 0.76)**

Intensive care unitc 83 4048 2.05 25 4277 0.58 0.29(0.24, 0.34)** 0.30(0.19, 0.47)**
65–74 30 2662 1.13 12 2910 0.41 0.37(0.30, 0.45)** 0.36(0.18, 0.71)**
75+ 53 1386 3.82 13 1367 0.95 0.25(0.19, 0.33)** 0.28(0.15, 0.51)**

Mortalityc 325 4085 7.96 134 4288 3.13 0.39(0.35, 0.45)** 0.44(0.36, 0.54)**
65–74 115 2675 4.30 50 2916 1.71 0.40(0.34, 0.47)** 0.40(0.29, 0.56)**
75+ 210 1410 14.89 84 1372 6.12 0.41(0.34, 0.50)** 0.46(0.35, 0.59)**
a
Rate, incidence rate, per 100 person-year.
b
IRR, incidence rate ratio.
c
Adjusted HR: adjusted for age, sex, and co-morbidities.
*
p < 0.05.
**
p < 0.01.

Several experimental studies have demonstrated a compara- only 49.0% in the diabetic adult group (18–64 years) and 69.9% in all
ble serological protection against influenza infection between DM elderly individuals in 2003 [25]. In Taiwan, the government began
patients and healthy control subjects [20,21]. Although the inci- to offer free influenza vaccinations to high-risk and elderly indi-
dence of serological non-responders was significantly increased in viduals in 1998. However, the average influenza vaccination rate
type 1 DM patients [20], the majority of DM patients can achieve an for elderly subjects was only 49.1% in 2007 [26]. Many physicians
appropriate humoral and cellular immune responses to influenza and patients are not convinced of the effectiveness of influenza
vaccination [22]. vaccination and are afraid of the adverse effects of the vaccina-
DM is a risk factor for pneumonia because these patients have tion. Inadequate knowledge and misconceptions lead to the low
an increased risk of aspiration, hyperglycemia, impaired immu- influenza vaccination coverage.
nity, decreased lung function, pulmonary microangiopathy, and The strengths of our study include the large representative
coexisting illnesses such as renal failure and heart disease [8]. DM sample size for the elderly, the cohort design, and the one-year
patients also have an increased risk of death from influenza and follow-up for each cohort. The one-year follow-up can determine
complicating pneumonia [9,23]. In the present study, influenza the possibility of delayed complications of influenza.
vaccination was associated with a significant reduction of 14% in The current study has several limitations. First, the NHID pro-
developing influenza or pneumonia. vided a limited amount of information on socio-demographic
According to the recommendations of the Advisory Committee characteristics, and information on marital status, educational
on Immunization Practices (ACIP), the influenza vaccine should be level, smoking habit, body-mass index, and laboratory data are
considered by DM patients >6 months annually [24]. Despite these unavailable. These variables cannot be adjusted in the analysis.
recommendations, the vaccination coverage was still much lower Furthermore, information on weights and height was also unavail-
than the 2010 health goal (90%). In the USA, the coverage rate was able for measuring the obesity status. However, these conditions
occurred in both groups. Moreover, the decision to receive vac-
cination may have been affected by socioeconomic status as well
Table 5 as the availability of health care and medical providers. Although
Stepwise regression analysis for hospitalization cost in the US dollars. multivariate analysis was used, selection bias may have occurred.
Variable Parameter Standard 95% CI Fourth, this study focused only on elderly DM patients because the
estimate error Taiwan government did not provide free influenza vaccination for
Intercept −5833.9 2852.9 (−11,426, −241.4)* population younger than 65 years of age. Our results may not be
Influenza vaccine −1282.6 473.3 (−2210.3, −354.8)** applicable to the younger population. In addition, some patients
Age 181.0 38.7 (105.2, 256.8)** with DM might be undiagnosed. A previous study in Taiwan found
Sex (male vs. female) 1137.3 478.3 (199.6, 2075.0)*
that approximately four percent of DM patients are undiagnosed
COPD 3235.4 496.5 (2262.2, 4208.7)**
Stroke 3863.7 517.8 (2848.8, 4878.7)** [27]. Finally, although we could not control for functional status
Atrial fibrillation 3435.9 1186.9 (1109.2, 5762.6)** like the study performed by Jackson et al. [28]. However, we were
Renal disease 1313.3 650.9 (37.3, 2589.2)* able to adjust for the variable of rehabilitation in the data analysis.
Hyperlipidemia −2763.3 496.7 (−3737.0, −1789.7)** In conclusion, our study provides evidence that influenza vacci-
Dementia 6721.6 976.4 (4807.5, 8635.7)**
CHF 4280.0 578.3 (3146.4, 5413.6)**
nation is associated with the reduction in the risk of hospitalization,
pneumonia or influenza, respiratory failure, ICU admission, and
Abbreviations: COPD, chronic obstructive pulmonary disease; CHF, congestive heart
death. In addition, the hospitalization cost is less. More large-
failure.
*
p < 0.05.
scale prospective studies are needed to investigate the efficacy of
**
p < 0.01. influenza vaccination.
724 I.-K. Wang et al. / Vaccine 31 (2013) 718–724

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