Advertisement
Browse Subject Areas
?

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here.

  • Loading metrics

Cross-sectional study on the prevalence of influenza and pneumococcal vaccination and its association with health conditions and risk factors among hospitalized multimorbid older patients

  • Dimitrios David Papazoglou ,

    Roles Conceptualization, Data curation, Formal analysis, Methodology, Visualization, Writing – original draft, Writing – review & editing

    papazoglou2019@gmail.com

    Affiliations Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland, Department of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland

  • Oliver Baretella,

    Roles Conceptualization, Data curation, Investigation, Writing – review & editing

    Affiliations Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland, Department of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland

  • Martin Feller,

    Roles Conceptualization, Methodology, Writing – review & editing

    Affiliation Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland

  • Cinzia Del Giovane,

    Roles Formal analysis, Methodology, Supervision, Validation, Writing – review & editing

    Affiliations Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland, Population Health Laboratory, University of Fribourg, Fribourg, Switzerland

  • Elisavet Moutzouri,

    Roles Conceptualization, Methodology, Writing – review & editing

    Affiliations Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland, Department of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland

  • Drahomir Aujesky,

    Roles Conceptualization, Methodology, Writing – review & editing

    Affiliation Department of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland

  • Matthias Schwenkglenks,

    Roles Methodology, Writing – review & editing

    Affiliation Institute of Pharmaceutical Medicine (ECPM), University of Basel, Basel, Switzerland

  • Denis O’Mahony,

    Roles Conceptualization, Supervision, Writing – review & editing

    Affiliations Department of Medicine Cork, University College Cork National University of Ireland, Munster, IE, Ireland, Department of Geriatric Medicine Cork, Cork University Hospital Group, Munster, IE, Ireland

  • Wilma Knol,

    Roles Conceptualization, Supervision, Writing – review & editing

    Affiliation Department of Geriatrics and Expertise Centre Pharmacotherapy in Old Persons (EPHOR), University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

  • Olivia Dalleur,

    Roles Conceptualization, Supervision, Writing – review & editing

    Affiliation Louvain Drug Research Institute, and Pharmacy Department, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium

  • Nicolas Rodondi,

    Roles Conceptualization, Supervision, Writing – review & editing

    Affiliations Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland, Department of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland

  • Christine Baumgartner

    Roles Conceptualization, Methodology, Supervision, Visualization, Writing – original draft, Writing – review & editing

    Affiliation Department of General Internal Medicine, Inselspital, Bern University Hospital, Bern, Switzerland

Cross-sectional study on the prevalence of influenza and pneumococcal vaccination and its association with health conditions and risk factors among hospitalized multimorbid older patients

  • Dimitrios David Papazoglou, 
  • Oliver Baretella, 
  • Martin Feller, 
  • Cinzia Del Giovane, 
  • Elisavet Moutzouri, 
  • Drahomir Aujesky, 
  • Matthias Schwenkglenks, 
  • Denis O’Mahony, 
  • Wilma Knol, 
  • Olivia Dalleur
PLOS
x

Abstract

Background

Older adults with chronic conditions are at high risk of complications from influenza and pneumococcal infections. Evidence about factors associated with influenza and pneumococcal vaccination among older multimorbid persons in Europe is limited. The aim of this study was to investigate the prevalence and determinants of these vaccinations in this population.

Methods

Multimorbid patients aged ≥70 years with polypharmacy were enrolled in 4 European centers in Switzerland, Belgium, the Netherlands, and Ireland. Data on vaccinations, demographics, health care contacts, and comorbidities were obtained from self-report, general practitioners and medical records. The association of comorbidities or medical contacts with vaccination status was assessed using multivariable adjusted log-binomial regression models.

Results

Among 1956 participants with available influenza vaccination data (median age 79 years, 45% women), 1314 (67%) received an influenza vaccination within the last year. Of 1400 patients with available pneumococcal vaccination data (median age 79 years, 46% women), prevalence of pneumococcal vaccination was 21% (n = 291). The prevalence of vaccination remained low in high-risk populations with chronic respiratory disease (34%) or diabetes (24%), but increased with an increasing number of outpatient medical contacts. Chronic respiratory disease was independently associated with the receipt of both influenza and pneumococcal vaccinations (prevalence ratio [PR] 1.09, 95% confidence interval [CI] 1.03–1.16; and PR 2.03, 95%CI 1.22–3.40, respectively), as was diabetes (PR 1.06, 95%CI 1.03–1.08; PR 1.24, 95%CI 1.16–1.34, respectively). An independent association was found between number of general practitioner visits and higher prevalence of pneumococcal vaccination (p for linear trend <0.001).

Conclusion

Uptake of influenza and particularly of pneumococcal vaccination in this population of European multimorbid older inpatients remains insufficient and is determined by comorbidities and number and type of health care contacts, especially outpatient medical visits. Hospitalization may be an opportunity to promote vaccination, particularly targeting patients with few outpatient physician contacts.

Introduction

Seasonal influenza is a contagious viral respiratory disease, which can cause mild to severe illness. Influenza affects approximately 4 to 50 million individuals and causes 15,000 to 70,000 deaths in the European Union (EU) each year [1]. Older persons and those with chronic medical conditions are most vulnerable of developing associated complications, which can lead to hospitalization and death [2, 3]. Health authorities from almost all EU countries recommend the influenza vaccination for individuals over 65 years of age independently of their comorbidities [4].

Manifestations of pneumococcal disease caused by infection with Streptococcus pneumoniae include community-acquired pneumonia, meningitis, as well as severe invasive pneumococcal disease. Pneumococcal disease is associated with high morbidity and mortality and is responsible for a larger number of deaths worldwide than influenza or HIV [5, 6]. The group most frequently affected by pneumococcal disease are children <2 years of age and adults older than 65 years, who are also at particularly high risk of associated mortality [7]. The pneumococcal vaccination is cost-effective in older individuals and can reduce invasive pneumococcal disease, pneumonia, and hospitalizations from pneumonia [813]. At present, most but not all European countries recommend pneumococcal vaccination for all individuals over 65 years of age independently of their comorbidities [14]. In other countries like Switzerland, pneumococcal immunization is recommended for patients with underlying diseases predisposing to invasive pneumococcal disease or at high risk for complications, for example those with chronic respiratory, cardiovascular, or kidney diseases, organ transplants, or haematologic malignancies [15].

Despite the known effectiveness of influenza and pneumococcal vaccination as a simple measure to reduce these diseases [16, 17], and the 75% European Centre for Disease Prevention and Control (ECDC) influenza vaccination coverage target for the EU in older people by 2015, actual coverage is much lower at around 45% [18]. Most studies examining factors associated with influenza and pneumococcal vaccination were conducted in Asia and America [1921], while fewer data exist on older individuals in European countries. Data on pneumococcal vaccination status in adults in Europe is particularly scarce [22]. Furthermore, we are aware of only a few smaller studies examining inappropriate lack of vaccination specifically among hospitalized multimorbid older patients who are at particularly high risk of subsequent influenza- and pneumococcal-associated morbidity and mortality [2325]. Identifying determinants of inappropriate lack of vaccination in this population is crucial for targeting public health interventions and reducing the burden of these potentially preventable diseases.

The aim of our study was to investigate the prevalence of influenza and pneumococcal vaccination in a population of multimorbid older inpatients and its determinants, taking advantage of baseline data from the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people) trial [26].

Materials and methods

Study design and participants

We conducted a cross-sectional study using baseline data from the OPERAM trial (ClinicalTrials.gov Identifier: NCT02986425). Details of the study design have been previously published [26]. In brief, OPERAM is a European multicenter cluster-randomized controlled trial investigating whether a medication optimization intervention during hospitalization compared to usual care can reduce the risk of drug-related hospital admissions among multimorbid older patients with polypharmacy. Overall, 2008 participants were recruited between December 2016 and October 2018 in four European university hospital centers in Switzerland, Belgium, the Netherlands, and Ireland. To be eligible for the OPERAM trial, patients had to be ≥70 years of age, multimorbid (defined as having ≥3 chronic health conditions) and had to take five or more chronic medications. Patients who were directly admitted to palliative care or those with a structured drug review within two months prior to screening were excluded from participation. We considered all OPERAM participants with available baseline data on vaccination status for the current study.

The local ethics committee at each of the participating sites approved the protocol of the OPERAM study (Cantonal Ethics Committee Bern, Switzerland; Medical Research Ethics Committee Utrecht, Netherlands; Comité d’Ethique Hospitalo-Facultaire Saint-Luc-UCL, Belgium; Cork University Teaching Hospitals Clinical Ethics Committee, Ireland). All participants or their legal representatives provided written informed consent.

Variables

Influenza and pneumococcal vaccination.

All data from the OPERAM trial were entered into a central database. To obtain information on vaccinations, the patient or next of kin were asked if and when the last influenza and pneumococcal vaccination was given. As the influenza vaccination needs to be administered annually, influenza vaccination status was coded as “yes” only if the influenza vaccination had been administered within 12 months before study inclusion. For the analysis of pneumococcal vaccination, all participants from the Netherlands were excluded as this information was not routinely collected.

Covariates.

Data on patient characteristics (age, sex, race, highest level of education, smoking status, and alcohol consumption) and use of medical resources (hospitalizations within the last year, visits to a general practitioner [GP], specialist, emergency department [ED], or hospital outpatient clinic within the last 6 months, nursing home stays or home nursing visits, or receipt of informal care [i.e., unpaid care by family members, relatives or friends] during the last 6 months) were collected at inclusion from the patient or next of kin.

We categorized the patients in clinical risk groups prone to a complicated or fatal course of influenza and pneumococcal infection. Definitions were taken from the infectious diseases “green book”, the immunization recommendations in the UK published by Public Health England, describing detailed clinical risk groups [27, 28]. These include patients with chronic respiratory disease, chronic heart disease, chronic kidney disease, chronic liver disease, diabetes, immunosuppression, and individuals with asplenia or dysfunction of the spleen, cochlear implants, or cerebrospinal fluid leaks. These clinical risk groups were coded using the International Statistical Classification of Diseases and Related Health Problems 10th revision (ICD-10) for health conditions and the Anatomical Therapeutic Chemical (ATC) Classification codes for medications as previously suggested [2932]. ICD-10 coded health conditions were obtained from discharge reports and only diagnoses with a diagnosis date less recent than the admission date were included. Information on medications using ATC codes was obtained from medical records, patient interview or pharmacy or GP lists. Medication data were used for the definition of diabetes and immunosuppression. Immunosuppression was defined as intake of at least 20mg of prednisone equivalent daily for more than a month and diabetes as the intake of any glucose-lowering agent as well as a corresponding ICD-10 code for diabetes mellitus. Due to the extremely low numbers of patients with asplenia or dysfunction of the spleen, cochlear implants, or cerebrospinal fluid leaks in our population, we did not investigate these clinical risk groups in our study.

The Charlson Comorbidity Index (CCI) to predict 10-year survival was calculated. The index ranges from 0 to 33, with lower scores indicating higher 10-year survival [33]. Quality of life was assessed using the European Quality of Life-5 Dimensions (EQ-5D) instrument. EQ-5D as a measure of generic, self-reported health status was administered following the rules of the EuroQol consortium. Country specific value sets were used to translate questionnaire responses to a health states measure on a 1 to 0 scale, with a value of 1 corresponding to perfect health and a value of 0 to death [3436]. The German value set was used for the Swiss study site in Bern and the French for the study site in Louvain, Belgium, due to missing value sets for these countries.

Statistical methods

We compared patient characteristics by receipt of influenza and pneumococcal vaccination using chi squared tests for categorical variables, and Student’s t-tests or Wilcoxon rank sum tests for continuous variables, as appropriate. Prevalence of influenza and pneumococcal vaccination overall and according to patient characteristics were calculated along with corresponding 95% confidence intervals (CI). To assess the association of chronic health conditions or use of medical resources with vaccination status, we used log-binomial regression models with vaccination status as the dependent variable and health conditions and variables for medical resource utilization as the main independent variables in separate models to compute unadjusted prevalence rate ratios and 95% CIs. We used log-binomial regression models because this is the recommended method to estimate prevalence ratios [37, 38]. We then adjusted these models for age, sex, race, education, alcohol use, and smoking status to investigate whether or not health conditions and medical resource utilization were associated with vaccination status independent of these variables. Furthermore, we clustered the analyses by study sites to take into account the participants’ correlation within each site, thus allowing for intragroup correlation of standard errors.

We carried out sensitivity analyses using Poisson regression models to assess the robustness of our results [37]. An additional sensitivity analysis for pneumococcal vaccination was done excluding patients from Switzerland, where national pneumococcal vaccination guidelines differ from those in the other two countries for which data on pneumococcal vaccination was available for our study participants. For these countries the pneumococcal vaccination is recommended in all patients aged 65 years or older; in Switzerland, the recommendation only applies to clinical risk groups with advanced chronic health conditions independent of their age (e.g. from COPD GOLD III, NYHA III, KDIGO G4) [15, 28, 39, 40].

We performed all statistical analyses using STATA version 13.1 (StataCorp, College Station, TX). Two-sided p-values of 0.05 were considered statistically significant. The STROBE statement was used for reporting this cross-sectional study [41].

Results

Of 2008 patients who were included in the OPERAM trial, 1956 multimorbid inpatients with available vaccination data were included in the analysis on influenza vaccination, and 1400 participants from three study sites were included in the analysis on pneumococcal vaccination. Of the 52 patients without available influenza data, 7 withdrew, and in 45 patients vaccination status was unknown. For the analysis of pneumococcal vaccination, all 452 participants from the Netherlands had to be excluded because this information had not been routinely collected at this study site. Of the remaining 1556 patients, 9 withdrew and information was lacking for 147 patients (Fig 1).

Table 1 shows baseline characteristics of the study population by influenza and pneumococcal vaccination status. Overall, the median age was 79 years [IQR 74–84] and 45% were women.

thumbnail
Table 1. Patient characteristics according to vaccination status.

https://doi.org/10.1371/journal.pone.0260112.t001

Influenza vaccination

Overall, 1314 of 1956 (67.2%) hospitalized multimorbid older patients were vaccinated against influenza within one year before study inclusion (Table 1). Median age was higher in the group with a positive compared to those with a negative influenza vaccination status (median age 79 years [IQR 75–85] vs. 77 years [IQR 73–82], while the percentage of women did not differ between the two groups (Table 1). Those who received an influenza vaccination were less likely to smoke (6.6% vs. 10.3%).

The probability of having received an influenza vaccination increased with age and with an increasing number of GP visits (p for trend both <0.001, Table 2). The prevalence of influenza vaccination was higher in individuals with low (less than high school, 71.3%) and high education levels (University, 68.6%) compared to those with an intermediate education level (high school, 64.0%). Above average influenza vaccination rates were seen in those with more comorbidities (CCI ≥ 7; 72.8%), patients receiving informal care within the last 6 months (73.6%) and in those with chronic respiratory (75.9%) and chronic kidney disease (77.3%).

thumbnail
Table 2. Vaccination prevalence according to population characteristics.

https://doi.org/10.1371/journal.pone.0260112.t002

In multivariable analysis, presence of chronic respiratory disease, chronic kidney disease and diabetes mellitus were independently associated with a higher prevalence of influenza vaccination, with adjusted prevalence ratios (PR) of 1.09 (95% CI 1.03–1.16), 1.12 (95% CI 1.08–1.17), and 1.06 (95% CI 1.03–1.08), respectively, while immunosuppression showed no association (Table 3). Specialist or ED visits in the last six months (PR 1.12, 95% CI 1.01–1.24 for ≥3 compared to no visit, p for linear trend 0.027) as well as a CCI ≥ 7 (PR 1.10, 95% CI 1.02–1.19) were associated with the receipt of influenza vaccination (Table 3).

thumbnail
Table 3. Association of chronic health conditions and medical resource utilization with receipt of influenza and pneumococcal vaccination.

https://doi.org/10.1371/journal.pone.0260112.t003

The results were similar in unadjusted analyses only considering clinical risk groups, health care contacts and health scores (S1 Table) and sensitivity analyses using Poisson regression models (S2 Table).

Pneumococcal vaccination

In the population of hospitalized multimorbid older patients with polypharmacy from 3 study sites (n = 1400), 20.8% (n = 291) were vaccinated against pneumococcal disease (Table 1). Patients with a pneumococcal vaccination were more likely to be female (52.9% vs. 44.3%) and to have a lower level of education compared to those without the vaccination (less than high school degree 42.6% vs. 26.7%), while age and smoking status were similar in both groups (Table 1).

The prevalence of pneumococcal vaccination was higher with an increasing number of GP visits and in those with ≥3 compared to those with <3 other outpatient physician or ED visits in the last 6 months (Table 2). Above average pneumococcal vaccination rates were seen in those receiving informal care (27.1%), those with chronic respiratory disease (34.3%), immunosuppression (27.4%), rheumatic disease (24.6%), and diabetes mellitus (23.7%).

A diagnosis of chronic respiratory disease, diabetes, or immunosuppression was associated with a higher prevalence of pneumococcal vaccination in multivariable adjusted analyses (PR 2.03, 95% CI 1.22–3.40; PR 1.24, 95% CI 1.16–1.34; and PR 1.29, 95% CI 1.03–1.61, respectively). Most other chronic health conditions investigated in our analysis including chronic heart, chronic liver or rheumatic disease and cancer, showed no association with pneumococcal vaccination, similar to the findings for influenza vaccination. GP visits within the last 6 months were very strongly associated with the receipt of pneumococcal vaccination (p for linear trend <0.001), showing a more than threefold higher prevalence of vaccination (PR 3.41, 95% CI 2.74–3.72) in those with 5 or more visits compared to those without GP visits within the last 6 months. The results were similar in unadjusted analyses, although chronic heart disease was associated with lower vaccination rates (S1 Table).

In a sensitivity analysis excluding all 453 patients from Switzerland, chronic respiratory disease, diabetes, immunosuppression and GP visits remained independently associated with higher pneumococcal vaccination rates, as was chronic liver disease (PR 1.04, 95% CI 1.01.-1.06) as well as a higher CCI (PR 1.25, 95% CI 1.15–1.37 for CCI ≥7 vs. CCI <7, S3 Table).

Discussion

In this population of multimorbid older inpatients aged ≥70 years with polypharmacy, 67% had received an influenza vaccination in the last 12 months, but only one in five persons had received a pneumococcal vaccination. Although patients with chronic respiratory disease and diabetes were more likely to be vaccinated, vaccination uptake in high risk groups remained insufficient. Outpatient medical contacts, particularly GP visits, were associated with a higher vaccination prevalence.

All participating countries recommend the influenza vaccination in all individuals aged 65 years or older [4]. The prevalence of influenza vaccination in our study was consistent with one cross-sectional study of hospitalized older patients in Spain and with estimates from the annual epidemiological survey by the European Centre for Disease Prevention and Control (ECDC) [23, 42]. According to the ECDC, the average influenza vaccination rates in the influenza season 2017–2018 were 47.1% in older age groups and 44.9% in individuals with chronic medical conditions; influenza vaccination rates in central European countries were mostly higher than 50% and in the UK over 60% [18]. The ECDC’s goal of 75% influenza vaccination rate in people above 65 years of age by 2015 has not been reached by any country in Europe [18], but some specific subgroups in our study have indeed vaccination uptakes near and over the ECDC’s goal. Specifically, we found high influenza vaccination coverage >75% among persons over 90 years (77.8%) as well as in those with chronic respiratory diseases (75.9%) and chronic kidney diseases (77.3%).

Overall, the prevalence of pneumococcal vaccination in our population of multimorbid older inpatients was very low with 20.8% and remained low in high risk population including those with chronic respiratory disease, immunosuppression, or chronic heart disease (all <35%). Pneumococcal vaccination coverage among older adults in European countries varies between 10% and 69% [22, 42, 43], although the available data is very limited [22]. The US office of disease prevention and health promotion set the Healthy People 2020 goal for pneumococcal vaccination uptake at 60% for at-risk adults aged <65 years and 90% for older people [44]; thus, the pneumococcal vaccination rates as found in our study and in other European countries are far off this goal [22, 42, 43].

Principal sociodemographic determinants of influenza and pneumococcal vaccination uptake in our study were older age, lower education, and non-smoking-status. These factors seem to positively influence vaccination uptake across different countries and cultures [19, 42, 43, 45, 46]. Although smoking is related to a wide range of chronic diseases it has been associated with lower influenza and pneumococcal vaccination rates in a large survey among community-dwelling older individuals in the United States [47]. These are at increased risk to suffer from the vaccine-preventable diseases under study and, consequently, vaccination rates should be higher in these groups [48, 49]. Further investigation is needed to unveil the reasons for not vaccinating, and efforts are necessary for promotion and education concerning vaccinations in this vulnerable group. Our results showed a U-shaped relationship between education and prevalence of influenza or pneumococcal vaccination. Previous studies have found inconsistent results between education and vaccination uptake, with some studies showing highest vaccination prevalence in individuals with low education and others in those with higher education [23, 45, 46]. Overall, the association is complex and differs according to population, culture, and health care system, and underlying factors merit further research.

An important factor influencing vaccination rates is chronic illness [46, 50]. Chronic respiratory disease showed the strongest association with vaccination rates in our and other studies [46, 50]. Both influenza and pneumococcal disease affect the lungs and are major triggers for exacerbations of asthma and chronic obstructive pulmonary disease (COPD) [51]. Therefore, it is probable that treating physicians recommend the vaccination especially to this vulnerable population. Other chronic illnesses associated with increased vaccination uptake were chronic kidney disease and diabetes mellitus, as previously observed in Switzerland [46]. Conversely, chronic heart disease showed no association with vaccination rates in our study, despite their increased risk to develop pneumococcal disease and its complications [7, 52] and the reduction of cardiovascular events with influenza vaccination in this group [53]. It has been previously observed that influenza vaccination rates are suboptimal in those with chronic heart disease [54], but not uniformly so. Recently published results from a population-based observational study from Catalonia showing a strong positive association between chronic heart disease and pneumococcal vaccination rates. This different result could be due to a stronger promotion of pneumococcal vaccination in Spain compared to other European countries [55]. Overall awareness should be raised for this vulnerable population. Similarly, we didn’t find any association of other high-risk group status with increased vaccination rates, like in those with chronic liver disease, rheumatic disease or malignant disease. Thus, the need in educating doctors about the indications and effectiveness of these vaccinations in high risk groups is still large, in order to prevent unnecessary and potentially preventable disease.

One of the most important factors associated with vaccination rates was the number and type of health care contacts. In line with previous results in hospitalized older patients [23], those with a higher number of GP and other outpatient medical visits were more likely to be vaccinated in our study. Previous studies have shown that the vaccination recommendations from medical staff, especially from GP’s, are among the strongest predictors for actual vaccination and it is the GP, who performs 93% of all vaccinations [20, 43, 50, 56, 57]. However, given the fact that a third of hospitalized multimorbid older patients are not up to date with their influenza vaccine and more than 75% of all high risk patients have not received the pneumococcal vaccinations, efforts are urgently needed to further educate physicians and to increase vaccination rates, particularly targeting patients with few outpatient physician contacts. This could be achieved by extensive patient and community-wide education for example by sending informational letters, as previously demonstrated in a Californian randomized trial [58], or provision of vaccination services at pharmacies. In addition, hospitalization for acute illness could be another opportunity to educate patients, and in the absence of acute contraindications, to vaccinate them, as vaccination is safe and effective in hospitalized patients and increases vaccination rates substantially as shown previously [5961].

Strengths and limitations

To the best of our knowledge this is the first study investigating influenza and pneumococcal vaccination rates and determinants for these vaccinations in hospitalized multimorbid, older people across different European countries. The main strength of our study is our large and high-quality data on comorbidities and the use of medical resources. In addition, it addresses older and multimorbid patients, a population that is underrepresented in clinical research.

Our study has some limitations. Hospitalized patients were included in this study, therefore these results might not translate to the general population. Vaccination information was self-reported, as it was in most other studies reporting influenza or pneumococccal vaccination rates [20, 50, 57]. Self-reporting has been shown to be a highly accurate method of assessing influenza vaccination status in older patients, but moderately accurate for pneumococcal vaccination, which is administered only once [62]. The prevalence of pneumococcal vaccination is underestimated by 5–10% when self-reported, as shown previously [63]. We cannot exclude that study power has been insufficient to detect statistically significant associations between influenza vaccination and numbers of GP visits, as well as pneumococcal vaccination and other outpatient physician / ED visits, as only non-statistically significant trends have been observed for these associations. Public financial support and reimbursement of vaccinations differ between countries (particularly for pneumococcal vaccination), which may have affected our results. Furthermore, we did not measure the number of pharmacy contacts as a potential determinant for receipt of vaccinations, given that they also provide these vaccinations. Another limitation is the cross-sectional design, which impedes any conclusion about the temporal relationship of patient characteristics and vaccination status.

Conclusion

Influenza and pneumococcal vaccination are determined by comorbidities as well as number and type of health care contacts, but uptake of these two vaccinations remains insufficient in this population of European multimorbid older inpatients. Our study showed that an increasing number of GP visits was strongly associated with a higher prevalence of pneumococcal vaccination, underlining the important role of the GP in the provision of recommended vaccinations. Further efforts are urgently needed to increase vaccination rates in these patients who are at particular high risk of complications from these potentially preventable diseases. Future interventions to promote appropriate vaccinations are needed, and hospitalization for acute illness could be taken as an opportunity to promote vaccination, particularly targeting patients with few outpatient physician contacts.

Supporting information

S1 Table. Association of chronic health conditions and medical resource utilization with receipt of influenza and pneumococcal vaccination.

https://doi.org/10.1371/journal.pone.0260112.s001

(DOCX)

S2 Table. Association of chronic health conditions and medical resource utilization with receipt of influenza and pneumococcal vaccination, calculated with Poisson regression model.

https://doi.org/10.1371/journal.pone.0260112.s002

(DOCX)

S3 Table. Association of chronic health conditions and medical resource utilization with receipt of pneumococcal vaccination excluding Switzerland.

https://doi.org/10.1371/journal.pone.0260112.s003

(DOCX)

References

  1. 1. European Centre for Disease Prevention and Control. Factsheet about seasonal influenza. 2019. https://www.ecdc.europa.eu/en/seasonal-influenza/facts/factsheet.
  2. 2. European Centre for Disease Prevention and Control. Seasonal influenza, 2017–2018. ECDC Annual epidemiological report for 2017. 2018.
  3. 3. Zhou H, Thompson WW, Viboud CG, Ringholz CM, Cheng PY, Steiner C, et al. Hospitalizations associated with influenza and respiratory syncytial virus in the United States, 1993–2008. Clin Infect Dis. 2012;54(10):1427–36. pmid:22495079
  4. 4. European Centre for Disease Prevention and Control. Influenza: Recommended vaccinations. 2019. https://vaccine-schedule.ecdc.europa.eu/Scheduler/ByDisease?SelectedDiseaseId=15&SelectedCountryIdByDisease=-1.
  5. 5. Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Infect Dis. 2018;18(11):1191–210. pmid:30243584
  6. 6. UNAIDS. Global HIV & AIDS statistics—Fact sheet. 2021. https://www.unaids.org/en/resources/fact-sheet.
  7. 7. European Centre for Disease Prevention and Control. Annual Epidemiological Report on Communicable Diseases in Europe 2009. Stockholm: European Centre for Disease Prevention and Control.
  8. 8. Domínguez A, Izquierdo C, Salleras L, Ruiz L, Sousa D, Bayas JM, et al. Effectiveness of the pneumococcal polysaccharide vaccine in preventing pneumonia in the elderly. European Respiratory Journal. 2010;36(3):608. pmid:20075048
  9. 9. Domínguez À, Salleras L, Fedson DS, Izquierdo C, Ruíz L, Ciruela P, et al. Effectiveness of pneumococcal vaccination for elderly people in catalonia, spain: A case-control study. Clinical Infectious Diseases. 2005;40(9):1250–7. pmid:15825026
  10. 10. Kawakami K, Ohkusa Y, Kuroki R, Tanaka T, Koyama K, Harada Y, et al. Effectiveness of pneumococcal polysaccharide vaccine against pneumonia and cost analysis for the elderly who receive seasonal influenza vaccine in Japan. Vaccine. 2010;28(43):7063–9. pmid:20723631
  11. 11. Maruyama T, Taguchi O, Niederman MS, Morser J, Kobayashi H, Kobayashi T, et al. Efficacy of 23-valent pneumococcal vaccine in preventing pneumonia and improving survival in nursing home residents: double blind, randomised and placebo controlled trial. BMJ. 2010;340:c1004. pmid:20211953
  12. 12. Vila-Córcoles A, Ochoa-Gondar O, Hospital I, Ansa X, Vilanova A, Rodríguez T, et al. Protective effects of the 23-valent pneumococcal polysaccharide vaccine in the elderly population: the EVAN-65 study. Clinical Infectious Diseases. 2006;43(7):860–8. pmid:16941367
  13. 13. Bonten MJM, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. New England Journal of Medicine. 2015;372(12):1114–25. pmid:25785969
  14. 14. Bonnave C, Mertens D, Peetermans W, Cobbaert K, Ghesquiere B, Deschodt M, et al. Adult vaccination for pneumococcal disease: a comparison of the national guidelines in Europe. Eur J Clin Microbiol Infect Dis. 2019;38(4):785–91. pmid:30778705
  15. 15. Bundesamt für Gesundheit, Eidgenössische Kommission für Impffragen. Schweizerischer Impfplan 2019. Richtlinien und Empfehlungen. Bern: Bundesamt für Gesundheit; 2019.
  16. 16. Moberley S, Holden J, Tatham DP, Andrews RM. Vaccines for preventing pneumococcal infection in adults. Cochrane Database of Systematic Reviews. 2013(1). pmid:23440780
  17. 17. Nichol KL, Nordin JD, Nelson DB, Mullooly JP, Hak E. Effectiveness of influenza vaccine in the community-dwelling elderly. New England Journal of Medicine. 2007;357(14):1373–81. pmid:17914038
  18. 18. European Centre for Disease Prevention and Control. Seasonal influenza vaccination and antiviral use in EU/EEA Member States—Overview of vaccine recommendations for 2017–2018 and vaccination coverage rates for 2015–2016 and 2016–2017 influenza seasons. Stockholm: ECDC; 2018.
  19. 19. Chan DPC, Wong NS, Wong ELY, Cheung AWL, Lee SS. Household characteristics and influenza vaccination uptake in the community-dwelling elderly: a cross-sectional study. Prev Med Rep. 2015;2:803–8. pmid:26844153
  20. 20. Kamal KM, Madhavan SS, Amonkar MM. Determinants of adult influenza and pneumonia immunization rates. Journal of the American Pharmacists Association. 2003;43(3):403–11. pmid:12836791
  21. 21. Wang Q, Yue N, Zheng M, Wang D, Duan C, Yu X, et al. Influenza vaccination coverage of population and the factors influencing influenza vaccination in mainland China: a meta-analysis. Vaccine. 2018;36(48):7262–9. pmid:30340886
  22. 22. Vila-Córcoles A, Ochoa-Gondar O, de Diego C, Satué E, Vila-Rovira A, Aragón M. Pneumococcal vaccination coverages by age, sex and specific underlying risk conditions among middle-aged and older adults in Catalonia, Spain, 2017. Euro Surveill. 2019;24(29):1800446.
  23. 23. Domínguez À, Soldevila N, Toledo D, Godoy P, Castilla J, Force L, et al. Factors associated with influenza vaccination of hospitalized elderly patients in Spain. PLOS ONE. 2016;11(1):e0147931. pmid:26824383
  24. 24. Ridda I, MacIntyre RC, Lindley RI, McIntyre PB, Sullivan J, Gilbert G, et al. Predictors of pneumococcal vaccination uptake in hospitalized patients aged 65 Years and over shortly following the commencement of a publicly funded national pneumococcal vaccination program in Australia. Human Vaccines. 2007;3(3):83–6. pmid:17361109
  25. 25. Ganczak M, Gil K, Korzeń M, Bażydło M. Coverage and influencing determinants of influenza vaccination in elderly patients in a country with a poor vaccination implementation. International Journal of Environmental Research and Public Health. 2017;14(6).
  26. 26. Adam L, Moutzouri E, Baumgartner C, Loewe AL, Feller M, M’Rabet-Bensalah K, et al. Rationale and design of OPtimising thERapy to prevent Avoidable hospital admissions in Multimorbid older people (OPERAM): a cluster randomised controlled trial. BMJ Open. 2019;9(6):e026769. pmid:31164366
  27. 27. Department of Health. Influenza: the green book, chapter 19. London: Public Health England; 2019.
  28. 28. Department of Health. Pneumococcal: the green book, chapter 25. London: Public Health England; 2019.
  29. 29. Australian Institute of Health and Welfare 2016. Australian Burden of Disease Study: Impact and causes of illness and death in Australia 2011. Canberra: Australian Institute of Health and Welfare; 2016.
  30. 30. Blumenfeld O, Na’amnih W, Shapira-Daniels A, Lotan C, Shohat T, Shapira OM. Trends in coronary revascularization and ischemic heart disease-related mortality in Israel. J Am Heart Assoc. 2017;6(2). pmid:28213569
  31. 31. Christiansen CF, Onega T, Svaerke C, Kormendine Farkas D, Jespersen B, Baron JA, et al. Risk and prognosis of cancer in patients with nephrotic syndrome. Am J Med. 2014;127(9):871–7.e1. pmid:24838191
  32. 32. Quan H, Sundararajan V, Halfon P, Fong A, Burnand B, Luthi J-C, et al. Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Medical Care. 2005;43(11). pmid:16224307
  33. 33. Mary Charlson. Charlson Comorbidity Index (CCI). 2019 15.11.2019. https://www.mdcalc.com/charlson-comorbidity-index-cci.
  34. 34. Ludwig K, Graf von der Schulenburg JM, Greiner W. German value set for the EQ-5D-5L. Pharmacoeconomics. 2018;36(6):663–74. pmid:29460066
  35. 35. Versteegh MM, Vermeulen MK, Evers MAAS, de Wit GA, Prenger R, Stolk AE. Dutch tariff for the five-level version of EQ-5D. Value Health. 2016;19(4):343–52. pmid:27325326
  36. 36. Andrade LF, Ludwig K, Goni JMR, Oppe M, de Pouvourville G. A french value set for the EQ-5D-5L. PharmacoEconomics. 2020;38(4):413–25. pmid:31912325
  37. 37. Barros AJD, Hirakata VN. Alternatives for logistic regression in cross-sectional studies: an empirical comparison of models that directly estimate the prevalence ratio. BMC Medical Research Methodology. 2003;3(1):21. pmid:14567763
  38. 38. Tamhane AR, Westfall AO, Burkholder GA, Cutter GR. Prevalence odds ratio versus prevalence ratio: choice comes with consequences. Stat Med. 2016;35(30):5730–5. pmid:27460748
  39. 39. Service public fédéral de la santé de Belgique. Vaccination antipneumococcique adultes. 08.01.2020. https://www.health.belgium.be/sites/default/files/uploads/fields/fpshealth_theme_file/19100960/Vaccination%20antipneumococcique%20-%20adultes%20%282014%29%20%28CSS%209210%29.pdf.
  40. 40. Control ECfDPa. Pneumococcal Disease: Recommended vaccinations. 2020. https://vaccine-schedule.ecdc.europa.eu/Scheduler/ByDisease?SelectedDiseaseId=25&SelectedCountryIdByDisease=-1.
  41. 41. von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies. PLOS Medicine. 2007;4(10):e296. pmid:17941714
  42. 42. Costello R, Winthrop KL, Pye SR, Brown B, Dixon WG. Influenza and pneumococcal vaccination uptake in patients with rheumatoid arthritis treated with immunosuppressive therapy in the UK: a retrospective cohort study using data from the clinical practice research datalink. PLoS One. 2016;11(4):e0153848. pmid:27096429
  43. 43. Schmedt N, Schiffner-Rohe J, Sprenger R, Walker J, von Eiff C, Hackl D. Pneumococcal vaccination rates in immunocompromised patients-A cohort study based on claims data from more than 200,000 patients in Germany. PLoS One. 2019;14(8):e0220848. pmid:31393931
  44. 44. The Office of Disease Prevention and Health Promotion. Healthy people 2020. Immunization and Infectious Diseases. 2019. https://www.healthypeople.gov/2020/topics-objectives/topic/Immunization-and-Infectious-Diseases/objectives#4670.
  45. 45. Santaularia J, Hou W, Perveen G, Welsh E, Faseru B. Prevalence of influenza vaccination and its association with health conditions and risk factors among Kansas adults in 2013: a cross-sectional study. BMC Public Health. 2016;16(1):185. pmid:26911615
  46. 46. Zuercher K, Zwahlen M, Berlin C, Egger M, Fenner L. Trends in influenza vaccination uptake in Switzerland: Swiss Health Survey 2007 and 2012. Swiss Med Wkly. 2019;149:w14705. pmid:30673116
  47. 47. Pearson WS, Dube SR, Ford ES, Mokdad AH. Influenza and pneumococcal vaccination rates among smokers: Data from the 2006 Behavioral Risk Factor Surveillance System. Preventive Medicine. 2009;48(2):180–3. pmid:19041339
  48. 48. Han L, Ran J, Mak YW, Suen LK, Lee PH, Peiris JSM, et al. Smoking and influenza-associated morbidity and mortality: a systematic review and meta-analysis. Epidemiology. 2019;30(3):405–17. pmid:30789425
  49. 49. Bagaitkar J, Demuth DR, Scott DA. Tobacco use increases susceptibility to bacterial infection. Tobacco Induced Diseases. 2008;4(1):12. pmid:19094204
  50. 50. Szucs TD, Muller D. Influenza vaccination coverage rates in five European countries-a population-based cross-sectional analysis of two consecutive influenza seasons. Vaccine. 2005;23(43):5055–63. pmid:16046035
  51. 51. Bekkat-Berkani R, Wilkinson T, Buchy P, Dos Santos G, Stefanidis D, Devaster J-M, et al. Seasonal influenza vaccination in patients with COPD: a systematic literature review. BMC Pulmonary Medicine. 2017;17(1):79. pmid:28468650
  52. 52. van Hoek AJ, Andrews N, Waight PA, Stowe J, Gates P, George R, et al. The effect of underlying clinical conditions on the risk of developing invasive pneumococcal disease in England. Journal of Infection. 2012;65(1):17–24. pmid:22394683
  53. 53. Udell JA, Zawi R, Bhatt DL, Keshtkar-Jahromi M, Gaughran F, Phrommintikul A, et al. Association between influenza vaccination and cardiovascular outcomes in high-risk patients: a meta-analysis. Jama. 2013;310(16):1711–20. pmid:24150467
  54. 54. Ajani UA, Ford ES, Mokdad AH. Examining the coverage of influenza vaccination among people with cardiovascular disease in the United States. American Heart Journal. 2005;149(2):254–9. pmid:15846262
  55. 55. European Centre for Disease Prevention and Control. Pneumococcal Disease: Recommended vaccinations. 2020. https://vaccine-schedule.ecdc.europa.eu/Scheduler/ByDisease?SelectedDiseaseId=25&SelectedCountryIdByDisease=-1.
  56. 56. Rehmet S, Ammon A, Pfaff G, Bocter N, Petersen LR. Cross-sectional study on influenza vaccination, Germany, 1999–2000. Emerg Infect Dis. 2002;8(12):1442–7. pmid:12498661
  57. 57. Burns VE, Ring C, Carroll D. Factors influencing influenza vaccination uptake in an elderly, community-based sample. Vaccine. 2005;23(27):3604–8. pmid:15855020
  58. 58. Szilagyi PG, Albertin C, Casillas A, Valderrama R, Duru OK, Ong MK, et al. Effect of patient portal reminders sent by a health care system on influenza vaccination rates: a randomized clinical trial. JAMA Intern Med. 2020. pmid:32421168
  59. 59. Berry BB, Ehlert DA, Battiola RJ, Sedmak G. Influenza vaccination is safe and immunogenic when administered to hospitalized patients. Vaccine. 2001;19(25):3493–8. pmid:11348716
  60. 60. Nowalk MP, Middleton DB, Zimmerman RK, Hess MM, Skledar SJ, Jacobs MA. Increasing pneumococcal vaccination rates among hospitalized patients. Infection Control & Hospital Epidemiology. 2003;24(7):526–31. pmid:12887242
  61. 61. McFadden K, Seale H. A review of hospital-based interventions to improve inpatient influenza vaccination uptake for high-risk adults. Vaccine. 2021;39(4):658–66. pmid:33357955
  62. 62. Mac Donald R, Baken L, Nelson A, Nichol KL. Validation of self-report of influenza and pneumococcal vaccination status in elderly outpatients. American Journal of Preventive Medicine. 1999;16(3):173–7. pmid:10198654
  63. 63. Collet T-H, Salamin S, Zimmerli L, Kerr EA, Clair C, Picard-Kossovsky M, et al. The quality of primary care in a country with universal health care coverage. Journal of general internal medicine. 2011;26(7):724–30. pmid:21424868