Original Research

Community acquired pneumonia: a cost-of-illness analysis in Greece

AUTHORS

Panagiota Naoum1 MSc, Researcher *

Kostas Athanasakis2 PhD, Researcher

Ilias Kyriopoulos3 PhD, Researcher

Adamantia Liapikou4 MD, Doctor

Michail Toumbis5 MD, Doctor

John Kyriopoulos6 PhD, Professor

CORRESPONDENCE

*Ms Panagiota Naoum

AFFILIATIONS

1, 2, 3, 6 Department of Health Economics, National School of Public Health, 196 Alexandras Av., 11521 Athens, Greece

4, 5 6th Pulmonary Clinic, Sotiria Chest Diseases Hospital, 152 Mesogion Av., 11527 Athens, Greece

PUBLISHED

15 June 2020 Volume 20 Issue 2

HISTORY

RECEIVED: 22 March 2019

REVISED: 7 May 2020

ACCEPTED: 11 May 2020

CITATION

Naoum P, Athanasakis K, Kyriopoulos I, Liapikou A, Toumbis M, Kyriopoulos J.  Community acquired pneumonia: a cost-of-illness analysis in Greece. Rural and Remote Health 2020; 20: 5400. https://doi.org/10.22605/RRH5400

AUTHOR CONTRIBUTIONSgo to url

This work is licensed under a Creative Commons Attribution 4.0 International Licence


abstract:

Introduction:  Community acquired pneumonia (CAP) is an acute respiratory infection with high clinical and economic burden, especially when hospitalisation is required. The present study aimed to assess the mean direct cost per CAP outpatient and inpatient care in Greece, in the absence of previous estimates.
Methods:  A retrospective analysis of patients at a tertiary hospital, treated between October 2015 and March 2016, was conducted. Resource use data for inpatients and outpatients were collected (diagnostic tests, medication, physician visits and length of hospitalisation, where applicable). Cost calculations followed a third party payer perspective. Additionally, two regression models were employed to identify the determinants of hospitalisation and the main drivers of inpatient and outpatient cost.
Results:  Overall, 149 inpatients and 100 outpatients were included in the analysis. Mean hospitalisation duration was 11.35 days (standard deviation (SD)=9.71 days). Mean direct cost per patient was €110.64 (SD=€58.23) and €7406.56 (SD=€12,124.93) for outpatient and inpatient cases respectively. (At the time period for the study, €1.00 was approximately A$1.50.) The main inpatient cost driver was hospitalisation (94.97%), followed by medication (3.30%) and diagnostic tests (0.87%). For outpatients, key cost drivers, in order of magnitude, were prescribed medication (38.84%), diagnostic tests (33.51%) and physician visits (17.54%). The regression analyses showed that the probability of hospitalisation increases with age and number of symptoms, whereas average cost is mainly influenced by gender, duration and number of symptoms, and the presence of comorbidities.
Conclusion:  The results indicate that, in Greece, CAP is accompanied by a significant economic burden, mainly attributable to hospitalisation. Interventions toward reducing the influence of contributors to the incidence and probability of hospitalisation are essential from a clinical and policy perspective. Also, the association of symptoms – in terms of number and duration – and age with hospitalisation probability and costs highlights that special attention should be given to the high risk groups of the population, such as the elderly and the rural residents, both in terms of preventive and therapeutic services.

Keywords:

CAP, community acquired pneumonia, cost of illness, economic burden, Greece

full article:

Introduction

Community acquired pneumonia (CAP) is an acute infection of the pulmonary parenchyma which occurs in people who do not live in long term care facilities and have not been hospitalised at least 14 days before the manifestation of symptoms, such as fever, rigors and cough1. Streptococcus pneumoniae is the pathogen most commonly identified as aetiologic factor of CAP, although various other pathogens can also cause the disease2,3.

Disease management largely depends on the individual clinical assessment of each patient. Typical symptoms indicating CAP are cough, dyspnoea, fever, chills, rigors and chest pain, and examination includes chest radiography, blood tests and oxygenation assessment4,5. Patients with low risk pneumonia are managed as outpatients, medium risk pneumonia requires hospitalisation, and high risk pneumonia usually requires admission to an intensive care unit (ICU)5.

CAP imposes a high disease burden to the population, with its incidence being higher in children and the elderly6,7. CAP mortality ranges between 1% and 48%8,9. The global burden of lower respiratory tract infections, which include CAP, has been estimated at 91.8 million disability-adjusted life years (DALYs), causing more than 2.3 million deaths worldwide in 20167. In Europe, CAP is the first cause of death related to infections and its incidence is expected to rise as the population ages10. In Greece, there has not been any organised effort to record and investigate the disease epidemiology at a national level. However, a recent study in a rural setting has estimated that hospitalisation rate for CAP patients amounts to 32%, and the median hospitalisation duration is 7 days11. In another study, the mean hospital stay for CAP in Greece was estimated at 9.6 days12.

As well as a high burden of disease, CAP entails a significant economic burden for health systems worldwide. In Europe, CAP costs more than €10.1 ($16.8) billion each year, with hospitalisation accounting for more than 50% of it, especially for elderly patients8,10. European studies have estimated a mean direct CAP cost per episode of between €432 and €1683 per hospitalised patient, while outpatient costs represented less than 10% of the total cost8,13,14. A comparative study across European countries showed that the mean hospitalisation cost per patient ranged from €1459.60 to €8443.89, while the corresponding cost for Greece was estimated at €3542.9212. (At the time period for the study, €1.00 was approximately A$1.50.)

Existing calculations for the economic burden of CAP in Greece have been based only on estimations rather than on real patient data, which are considered a more efficient tool for such analyses. Using primary patient data, this analysis thus aimed to estimate the cost per inpatient and outpatient of CAP in Greece based on the official resource prices of the Greek healthcare system. The study also aimed to investigate factors associated with the probability of hospitalisation and the determinants of inpatient and outpatient costs.

Methods

Data were collected from the Athens General Hospital for Chest Diseases (Sotiria), a national centre for pulmonary diseases, in collaboration with the 6th Pulmonary Clinic of the hospital.

Primary data for the analysis were based on a retrospective study of patients who visited the outpatient department of a tertiary hospital in Athens, Greece, with pneumonia symptoms. The data collection period was between October 2015 and March 2016, which coincides with the high incidence period in Greece. Inclusion criteria were (1) definitive diagnosis of community acquired pneumonia by the treating physician based on the necessary diagnostic tests, (2) eligible patients being at least 18 years of age and (3) patient capacity to consent. Exclusion criterion, according to the disease definition, was hospitalisation during the last 14 days before symptoms emerged1.

For each patient diagnosed with CAP, resource use patterns were collected. Resource use categories for estimating the inpatient care cost were diagnostic tests, medication, hospital stay duration, additional laboratory and radiographic tests during hospitalisation and discharge instructions. To calculate the cost in outpatient level, the analysis considered the following resource use categories: diagnostic tests, medication dosage and duration, and hospital visits. Moreover, the dataset included information on whether patients of both groups returned for reassessment. If this was the case, it further recorded the additional tests and medication they were provided. Further data collected in the study included age, smoking status, comorbidities, symptoms that led to the hospital visit and duration of symptoms before visiting the hospital.

Cost calculations were performed from a third party payer perspective, so only direct costs were estimated, while unit costs refer to 2016. The cost (C) for each resource use category derived from the official price bulletin of the third party payer and the total costs were estimated as follows:

Cinpatient = Cdiagnostics + Cmedication + Chospital stay + Cadditional tests + Creassessment

Coutpatient = Cdiagnostics + Cmedication + Chospital visits + Creassessment

Specifically, the cost units for laboratory and imaging tests derived from the official state prices issued by the Greek National Organisation for Healthcare Services Provision15, while the unit costs for medication were sourced from the Official Medication Price Bulletins which effective during the study period16,17. Concerning hospitalisation cost, unit costs derived from the Greek Diagnosis-Related Group system costs18, adjusted for hospital stay longer than the average expected in the system as well as for staff salaries, which are not incorporated in the cost system, and discounted at present values with a 3% discount rate.

Apart from estimating the costs, the present analysis aimed to uncover the factors associated with the probability of hospitalisation. In doing so, a logistic regression model was employed, and the dependent variable of the analysis was inpatient admission (value of 1 if the patient was admitted to hospital, or 0 if CAP was treated in outpatient care). Further, this analysis focused on the determinants of inpatient and outpatient costs. Taking into account the distributional characteristics of healthcare costs, this study employed a linear regression model with a log-transformed dependent variable. The independent variables of the analysis were: gender, duration of symptoms, age, smoking, presence of comorbidities and number of symptoms.

Ethics approval

All necessary ethics approvals were obtained from the Scientific Committee of Athens General Hospital for Chest Diseases (Sotiria), as well as from the Bioethics and Research Ethics Committee of the National School of Public Health in Athens (1029/24.7.2015).

Results

Sample characteristics

The study sample consisted of 249 patients, 149 of whom were hospitalised (59.8%) and 100 were treated as outpatients (Table 1). The mean age of the total sample was 55.1 (standard deviation (SD)=18.764) years, while separately it was 61.4 (SD=16.80) years and 45.8 (SD=17.66) years for the inpatients and outpatients respectively. Additionally, 53.3% of the total sample were current smokers. As shown in Table 1, 67.8% of the hospitalised patients and 42.0% of the outpatients had a chronic health condition, with pulmonary and circulatory diseases being the most common for both patient subgroups.

Before visiting the hospital’s outpatient department, 71.7% of the sample had on average two to three coexisting symptoms, with fever, cough and shortness of breath being most commonly reported (Table 1). Mean duration of symptoms before hospital visit amounted to 4.8 (SD=3.054) days, ranging from 1 to 15 days of sickness.

Table 1:  Study sample characteristicstable image

Resource use, cost analysis and regression results 

In order to be diagnosed, every patient in the sample had a face X-ray and a general blood test. Additionally, a set of biochemical tests (eg urea, creatinine, alkaline phosphatase) was performed in 85.8% of the sample and profile X-ray in 80.3% of the sample, as presented in Table 1. Apart from general blood test and face X-ray, all diagnostic tests were performed at a much greater frequency for those who were hospitalised upon diagnosis.

Out of the 149 hospitalised CAP patients, 91.3% were treated in the general ward and 8.7% required admission to the ICU. The mean length of stay was estimated at 11.35 (SD=9.170) days, ranging from 1 to 70 days. Mean length of stay for the patients admitted to the regular hospital clinic was 10.21 days (SD=7.200). For the subgroup of patients admitted to the ICU, the mean length of stay was much greater, approximately 23.38 (SD=20.197) days, 16.08 (SD=14.068) days of which were in the ICU and 7.30 (SD=7.952) days in the regular clinic.

During their stay in hospital, all inpatients were submitted to face X-ray, with a mean of 3.34 (SD=3.670) X-rays per patient; 92.6% to profile X-ray, with a mean of 1.77 (SD=1.179) X-rays per patient; and 99.3% to a general blood test. with a mean of 3.10 (SD=2.288) tests per patient (Table 2). A total of 99.3% of all inpatients were discharged (n=148) (one patient died in hospital) and 35.8% were prescribed further medication. Only 3.37% returned to the hospital for reassessment within a week after discharge, all of whom were submitted to face X-ray and all but one to profile X-ray. Of the outpatients, 95.0% revisited the hospital for reassessment of their condition. Face X-ray was performed for all patients, profile X-ray for 24.2% and thorax computed tomography for 7.4%.

For inpatients, the cost analysis included cost of diagnostic tests, hospital stay, medication during hospitalisation, blood and radiographic tests during hospitalisation, medication prescribed upon discharge and reassessment tests (if readmitted to the hospital). For outpatients, cost of hospital visits, diagnostic tests, prescribed medication, reassessment tests and additional medication after reassessment were calculated.

Hospital stay accounted for the greatest part of the inpatient cost, and admission to the ICU represented 37.0% of total hospital stay cost. Average cost per hospitalised patient was estimated at €7406.56 ($12,322.46), while the corresponding cost per patient in outpatient care was approximately €110.64 ($184.07) (Table 3).

Model 1 in Table 4 shows that the odds of hospitalisation for an elderly person are three times the odds of hospitalisation for an individual aged less than 65 years. In addition, the number of symptoms is positively associated with hospitalisation, whereas there was no statistically significant relationship between comorbidity and the probability of hospitalisation. Figure 1 indicates how the predicted probability of hospitalisation changes with age, while Figure 2 shows that the probability of hospitalisation increases with number of symptoms. According to Table 4 (Model 2), males tend to have higher hospitalisation costs compared to females, and the duration and number of symptoms are both positively associated with inpatient costs. For outpatient cost, comorbidity is a statistically significant determinant.

Table 2:  Frequency of testing and mean number of tests per patienttable image

Table 3:  Cost per patient and cost distribution per categorytable image

Table 4:  Study regression modelstable image

table image Figure 1:  Predicted probability of hospitalisation, by age.

table image Figure 2:  Predicted probability of hospitalisation, by number of symptoms.

Discussion

Community acquired pneumonia is a disease associated with high clinical and economic burden. The management of CAP patients and its derived cost mainly depend on the need for hospitalisation, based on the severity of the disease.

In general, the sample characteristics of this analysis (eg respondents’ age, smoking status and comorbidities) are similar to the ones recorded in other studies11, while hospitalised individuals are generally older compared to the patients using outpatient care. In addition, all disease symptoms – and especially shortness of breath – are more frequent for hospitalised patients. Both of these findings are supported by the regression model for hospitalisation, which is potentially indicative of the reasoning behind physicians’ decisions about whether patients are admitted for hospitalisation or not.

As already mentioned, diagnostic tests were found to be generally performed more frequently for hospitalised patients. This finding can be potentially attributed to their clinical condition at the time of hospital visit and to their older age. Nevertheless, all patients were submitted to face X-ray and general blood test, which is the standard clinical practice for the diagnosis of pneumonia and reported in previous research19. A potential interpretation for the high rate of hospital admissions within the sample potentially relates to the fact that patients quite significantly delayed their visit to the hospital. A significant mean duration (7 days) of symptoms before hospital admission has been also observed in a relevant previous study20.

The analysis for the two patient subgroups demonstrates significant differences between outpatients and inpatients both in clinical and economic terms. Regarding outpatients, it is clear that their treatment only includes diagnostic tests and medication – usually with the patient participating to the respective cost – while virtually the only challenge for the hospital and the treating physician is to ensure the patients’ return for reassessment of their condition and the effectiveness of the therapy.

The clinical management of hospitalised patients is more complicated as it entails various therapeutic means, due to the severity of the patients’ condition, while hospital stay is the main driving factor of the inpatient cost, especially when admission to ICU is required21. This finding is in line with previous research, as hospital stay accounts for 61.0–94.3% of the total inpatient CAP cost22-24. Apart from the economic burden, hospitalised patients are at risk of in-hospital infections, which can further worsen their condition and lead to longer duration of hospitalisation.

The mean hospitalisation duration of the present study (11.35 days) is higher than that reported by other studies in Greek settings, which have estimated mean hospitalisation durations of 715 and 9.6 days12. Nevertheless, relevant research findings in other European countries support the present findings, estimating a mean length of stay at 1219, 12.125 and 14.62 days20. Furthermore, the present study estimated a lower rate of ICU admission (8.7%) compared to a recent study where 22.7% of hospitalised CAP patients were admitted to ICU[24}, but a higher mean length of stay in ICU (16.08 days) compared to 5.1 and 7 days estimated elsewhere24,26. Given that ICU stay has been found to influence hospital costs27, it could partially explain the higher cost per patient calculated in the present study. Also, the finding that the duration and number of symptoms are positively associated with inpatient cost is expected, as they indicate a worse clinical condition, which leads to more intensive health care.

Additionally, the outpatient cost represents only a small fraction of the total CAP cost (1.47%), which aligns with other study findings14,21,28. Regarding outpatients, the main cost drivers were medication and diagnostic examinations, which is in line with previous relevant research23.

In the face of the demographic transition that is observed globally, especially in the developed world, the burden of CAP is expected to steeply increase. Respiratory infections are one of the leading causes of morbidity and mortality globally, with Streptococcus pneumoniae accounting for more deaths than all other respiratory aetiologies combined29. However, although there is a reduction of the global respiratory infection burden, improving the disease ranking (fourth in 2017 compared to third in 1990)29,30, in Greece there is an opposite development (six in 2017 compared to ninth in 1990)31,32. Bearing in mind the fact that older people often have underlying conditions, the proportion of complicated CAP patients requiring hospitalisation is also expected to increase33, unless an effective strategy against the disease is adopted.

Greece is a country with a significant proportion of the population dispersed in its rural parts, usually of higher age, as reported in the most recent national census34. Also, healthcare services are unevenly distributed across the country, as they are highly concentrated in a handful of large cities, while almost half of the country’s hospitals and healthcare professionals reside in the capital, Athens35. As a result, the rural population face obstacles in their access to healthcare services36-38. In the case of pneumonia, as well as other infections and diseases for which timely diagnosis is vital to the overall treatment and prognosis of the patient, these obstacles are most likely to cause a significant delay in seeking and/or reaching healthcare services39. This leads to a higher probability of the patient presenting with a worse clinical condition and a higher probability of hospitalisation with its accompanying costs. The results of the present study, which despite its urban setting noted a remarkably high proportion of patients requiring hospitalisation, raise concerns about how much worse the situation might be in rural parts of Greece. Although there are no data available on the residents of the sample, it has been highlighted elsewhere that the majority of rural residents in Greece prefer to travel long distances to use urban care services instead of rural ones, which suggests that a proportion of the present study sample comes from rural areas40.

In general, CAP can be prevented on a large scale with proper vaccination41. Nowadays, a few different vaccines are available, which are effective in the prevention of the disease42. The influenza and pneumococcal vaccines have been extensively studied as preventive tools against CAP occurrence. The existing findings suggest that the use of vaccines on different groups of the population, either alone or combined, can successfully reduce the incidence of the disease11,43,44 and lead to reduced hospitalisation rates and lower length of hospital stay19. Apart from clinical effectiveness, existing evidence demonstrates that vaccination against pneumonia is also cost effective, when specific population groups (eg infants and elderly) are vaccinated45-47.

Despite the wide availability of effective vaccines, their optimal use is yet to be achieved48-50, while a nationwide health survey in Greece has reported that less than 20% of the adult population is vaccinated within the recommended timeframe51. In order to achieve an adequate uptake of vaccination in Greece, the formation of an organised vaccination program is considered necessary. Given the high proportion of the population residing in rural regions, mobile units should be available to reach the remote parts of the country and especially the elderly.

Study strengths and limitations

The present study was conducted in a national referral hospital for respiratory diseases, which indicates that the study sample is quite representative of the overall population. However, the small sample size limits the external validity for generalisability of the results. Furthermore, the study does not include indirect costs, such as productivity losses, which have been identified as an important source of cost in previous research20.

Implications

Based on these study results and bearing in mind the current economic environment in Greece, it is very important for the national health system to identify and encounter avoidable cost sources. As described in the present analysis, in the case of CAP, this source is mainly identified in hospitalisation. Consequently, information for and education of the public are essential so that people are aware of the importance of vaccination against the disease, especially for vulnerable and remote groups of the population. Timely identification of CAP symptoms and prompt referral to a physician would contribute to reduction of avoidable hospitalisations. Further research on the inequalities of healthcare access and utilisation between different groups of the population would potentially reveal shortcomings of the healthcare system that should be addressed.

Conclusion

The results of the present study highlight the fact that CAP is a disease that is a significant economic burden on the Greek healthcare system, the main determinant of which is hospitalisation rates and duration. Interventions toward reducing the influence of the contributors to the incidence and probability of hospitalisation are essential from a clinical and policy perspective. Furthermore, hospitalisation rates and overall costs have been found to be associated with number and duration of symptoms.

The findings of the present study highlight the attention that should be given to high risk populations, especially the elderly, as well as those who reside in remote areas of Greece, regarding the prevention of the disease, mainly through vaccination, and access to proper and timely health services.

references:

1 Bartlett JG, Dowell SF, Mandell LA, File TM Jr, Musher DM, Fine MJ. Practice guidelines for the management of community-acquired pneumonia in adults. Clinical Infectious Diseases 2000; 31: 347-382. https://doi.org/10.1086/313954 PMid:10987697
2 Lode HM. Managing community-acquired pneumonia: a European perspective. Respiratory Medicine 2007; 101: 1864-1873. https://doi.org/10.1016/j.rmed.2007.04.008 PMid:17548187
3 Drijkoningen JJC, Rohde GGU. Pneumococcal infection in adults: burden of disease. Clinical Microbiology and Infection 2014; 20(5): 45-51. https://doi.org/10.1111/1469-0691.12461 PMid:24313448
4 Johnson PDR, Irving LB, Turnidge JD. Community-acquired pneumonia. Medical Journal of Australia 2002; 176(7): 341-347. https://doi.org/10.5694/j.1326-5377.2002.tb04437.x PMid:12013330
5 Patterson CM, Loebinger MR. Community acquired pneumonia: assessment and treatment. Clinical Medicine (London) 2012; 12(3): 283-286. https://doi.org/10.7861/clinmedicine.12-3-283 PMid:22783785
6 Rudan I, Tomaskovic L, Boschi-Pinto C, Campbell H. Global estimate of the incidence of clinical pneumonia among children under five years of age. Bulletin of the World Health Organization 2004; 82(12): 895-903.
7 Institute for Health Metrics and Evaluation. GBD – Global Burden of Disease Study (2016) Results. 2017. Available: http://ghdx.healthdata.org/gbd-results-tool (Accessed 24 January 2019).
8 Welte T, Torres A, Nathwani D. Clinical and economic burden of community-acquired pneumonia among adults in Europe. Thorax 2010; 67: 71-79. https://doi.org/10.1136/thx.2009.129502 PMid:20729232
9 Spoorenberg SMC, Bos WJW, Heijligenberg R, Voorn PG, Grutters JC, Rijkers GT, et al. Microbial aetiology, outcomes, and costs of hospitalization for community-acquired pneumonia; an observational analysis. BMC Infectious Diseases 2014; 14: 335. https://doi.org/10.1186/1471-2334-14-335 PMid:24938861
10 Blasi F, Mantero M, Santus PA, Tarsia P. Understanding the burden of pneumococcal disease in adults. Clinical Microbiology and Infection 2012; 18(5): 7-14. https://doi.org/10.1111/j.1469-0691.2012.03937.x PMid:22882668
11 Bertsias A, Tsiligianni IG, Duijker G, Siafakas N, Lionis C. Studying the burden of community-acquired pneumonia in adults aged ≥50 years in primary health care: an observational study in rural Crete, Greece. NPJ Primary Care Respiratory Medicine 2014; 24: 14017. https://doi.org/10.1038/npjpcrm.2014.17 PMid:24965889
12 Ostermann H, Garau J, Medina J, Pascual E, McBride K, Blasi F. Resource use by patients hospitalized with community-acquired pneumonia in Europe: analysis of the REACH study. BMC Pulmonary Medicine 2014; 14: 36. https://doi.org/10.1186/1471-2466-14-36 PMid:24593248
13 Reyes S, Martinez R, Vallés JM, Cases E, Menendez R. Determinants of hospital costs in community-acquired pneumonia. European Respiratory Journal 2008; 31: 1061-1067. https://doi.org/10.1183/09031936.00083107 PMid:18448502
14 Tichopad A, Roberts C, Gembula I, Hajek P, Skoczynska A, Hryniewicz W, et al. Clinical and economic burden of community-acquired pneumonia among adults in the Czech Republic, Hungary, Poland and Slovakia. PLoS ONE 2013; 8(8): e71375. https://doi.org/10.1371/journal.pone.0071375 PMid:23940743
15 The National Organization for the Provision of Health Services. Medical service categories. [In Greek]. Available: https://eopyyfiles.blob.core.windows.net/eopyysite/ServiceCategories/cd5ce111-b348-44a1-8fad-deb203b8f8b5.pdf (Accessed 10 October 2018).
16 Hellenic Ministry of Health. Correction bulletin for Medication Price List. [In Greek]. Available: http://www.moh.gov.gr/articles/times-farmakwn/deltia-timwn/4066-diorthwtiko-deltio-timwn-farmakwn-anthrwpinhs-xrhshs-anatimologhsh-25-7-2016 (Accessed 10 October 2018).
17 Hellenic Ministry of Health. Price List for New Medicines. [In Greek]. Available: http://www.moh.gov.gr/articles/times-farmakwn/deltia-timwn/4205-deltio-timwn-farmakwn-anthrwpinhs-xrhshs-newn-farmakwn (Accessed 10 October 2018).
18 Greek Diagnostic Related Groups System. Investigation of Closed Understanded Nursing (KEN). [In Greek]. Available: http://kenicd.e-healthnet.gr/.aspx (Accessed 10 October 2018).
19 McCarthy H, O’Donnell S, Costello RW, Humphreys H. Hospital resource utilisation by patients with community-acquired pneumonia. Iranian Medical Journal 2017; 110(7): 613.
20 Cupurdija V, Lazic Z, Petrovic M, Mojsilovic S, Cekerevac I, Rancic N, et al. Community-acquired pneumonia: economics of inpatient medical care vis-à-vis clinical severity. Jornal Brasileiro de Pneumologia 2015; 41(1): 48-57. https://doi.org/10.1590/S1806-37132015000100007 PMid:25750674
21 Jakovljevic M, Cupurdija V, Lazic Z. Cost of illness of community-acquired pneumonia. Review of the literature and possible strategies in the Serbian health care setting. Farmeconomia. Health Economics and Therapeutic Pathways 2012; 13(3): 133-139. https://doi.org/10.7175/fe.v13i3.275
22 Orrick JJ, Segal R, Johns TE, Russell W, Wang F, Yin DD. Resource use and cost of care for patients hospitalised with community acquired pneumonia: impact of adherence to Infectious Diseases Society of America guidelines. Pharmacoeconomics 2004; 22(11): 751-757. https://doi.org/10.2165/00019053-200422110-00005 PMid:15250752
23 Konomura K, Nagai H, Akazawa M. Economic burden of community-acquired pneumonia among elderly patients: a Japanese perspective. Pneumonia 2017; 9: 19. https://doi.org/10.1186/s41479-017-0042-1 PMid:29226070
24 Divino V, Schranz J, Early M, Shah H, Jiang M, DeKoven M. The annual economic burden among patients hospitalized for community-acquired pneumonia (CAP): a retrospective US cohort study. Current Medical Research and Opinion 2020; 36(1): 151-160. https://doi.org/10.1080/03007995.2019.1675149 PMid:31566005
25 Vissink CE, Huijts SM, de Wit A, Bonten MJM, Mangen MJJ. Hospitalization costs for community-acquired pneumonia in Dutch elderly: an observational study. BMC Infectious Diseases 2016; 16(1): 466. https://doi.org/10.1186/s12879-016-1783-9 PMid:27589847
26 Gümüş A, Çilli A, Çakın Ö, Karakurt Z, Ergan B, Aksoy E, et al. Factors affecting cost of patients with severe community-acquired pneumonia in intensive care unit. Turkish Thoracic Journal 2019; 20(4): 216-223. https://doi.org/10.5152/TurkThoracJ.2018.18084 PMid:31390327
27 Cortoos PJ, Gilissen C, Laekeman G, Peetermans WE, Leenaers H, Vandorpe L, et al. Length of stay after reaching clinical stability drives hospital costs associated with adult community-acquired pneumonia. Scandinavian Journal of Infectious Diseases 2013; 45(3): 219-226. https://doi.org/10.3109/00365548.2012.726737 PMid:23113827
28 Colice GL, Morley MA, Asche C, Birnbaum HG. Treatment costs of community-acquired pneumonia in an employed population. Chest 2004; 125: 2140-2145. https://doi.org/10.1378/chest.125.6.2140 PMid:15189934
29 Global Burden of Disease 2016 Lower Respiratory Infections Collaborators. 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 Infectious Diseases 2018; 18(11): 1191-1210.
30 Institute for Health Metrics and Evaluation. GBD compare: Global, both sexes, all ages, deaths per 100,000, 1990 and 2017 rank. Available: http://ihmeuw.org/4srx (Accessed 3 April 2020).
31 Global Burden of Disease 2016 Greece Collaborators. The burden of disease in Greece, health loss, risk factors, and health financing, 2000-16: an analysis of the Global Burden of Disease Study 2016. Lancet Public Health 2018; 3: e395-e406.
32 Institute for Health Metrics and Evaluation. GBD compare: Greece, both sexes, all ages, deaths per 100,000, 1990 and 2017 rank. Available: http://ihmeuw.org/5310 (Accessed 3 April 2020).
33 Wroe PC, Finkelstein JA, Ray GT, Linder JA, Johnson KM, Rifas-Shiman S, et al. Aging population and future burden of pneumococcal pneumonia in the United States. Journal of Infectious Diseases 2012; 205(10): 1589-1592. https://doi.org/10.1093/infdis/jis240 PMid:22448012
34 Hellenic Statistical Authority. Demographic and social characteristics of the resident population of Greece according to the 2011 Population – Housing Census revision of 20/3/2014. Piraeus: Hellenic Statistical Authority, 2014.
35 OECD/European Observatory on Health Systems and Policies. Greece: Country Health Profile 2017. State of Health in the EU profile. Brussels: OECD Publishing, Paris/European Observatory on Health Systems and Policies, 2017. https://doi.org/10.1787/9789264283404-en
36 Goodridge D, Lawson J, Rennie D, Marciniuk D. Rural/urban differences in health care utilization and place of death for persons with respiratory illness in the last year of life. Rural and Remote Health 2010; 10(2): 1349. Available: http://www.rrh.org.au/journal/article/1349 (Accessed http://www.rrh.org.au/journal/article/1349).
37 Douthit N, Kiv S, Dwolatzky T, Biswas S. Exposing some important barriers to health care access in the rural USA. Public Health 2015; 129(6): 611-620. https://doi.org/10.1016/j.puhe.2015.04.001 PMid:26025176
38 Zhang X, Dupre ME, Qiu L, Zhou W, Zhao Y, Gu D. Urban-rural differences in the association between access to healthcare and health outcomes among older adults in China. BMC Geriatrics 2017; 17: 151. https://doi.org/10.1186/s12877-017-0538-9 PMid:28724355
39 Vavouranakis I, Fanioudaki A, Lamprogiannakis E, Baltzakis I, Sidiropoulou K, Porfiri E, et al. Delays incurred during acute myocardial infarction: a comparative study of rural and urban populations in Greece. Rural and Remote Health 2010; 10(2): 1271. Available: http://www.rrh.org.au/journal/article/1271 (Accessed 20 July 2019).
40 Oikonomou N, Tountas Y. Insufficient primary care services to the rural population of Greece. Rural and Remote Health 2011; 11: 1661. Available: http://www.rrh.org.au/journal/article/1661 (Accessed 5 April 2020).
41 Simberkoff MS and Santos MR. Prevention of community-acquired and nosocomial pneumonia. Current Opinion in Pulmonary Medicine 1996; 2(3): 228-235. https://doi.org/10.1097/00063198-199605000-00011 PMid:9363144
42 Principi N, Esposito S. Prevention of community-acquired pneumonia with available pneumococcal vaccines. International Journal of Molecular Sciences 2017; 18(1): 30. https://doi.org/10.3390/ijms18010030 PMid:28029140
43 Christenson B, Hedlund J, Lundbergh P, Ortqvist A. Additive preventive effect of influenza and pneumococcal vaccines in elderly persons. European Respiratory Journal 2004; 23(3): 363-368. https://doi.org/10.1183/09031936.04.00063504 PMid:15065822
44 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: 1114-1125. https://doi.org/10.1056/NEJMoa1408544 PMid:25785969
45 Weaver M, Krieger J, Castorina J, Walls M, Ciske S. Cost-effectiveness of combined outreach for the pneumococcal and influenza vaccines. Archives of Internal Medicine 2001; 161(1): 111-120. https://doi.org/10.1001/archinte.161.1.111 PMid:11146707
46 Cai L, Uchiyama H, Yanagisawa S, Kamae I. Cost-effectiveness analysis of influenza and pneumococcal vaccinations among elderly people in Japan. Kobe Journal of Medical Sciences 2006; 52(3-4): 97-109.
47 Thorrington D, van Rossum L, Knol M, de Melker H, Rümke H, Hak E, et al. Impact and cost-effectiveness of different vaccination strategies to reduce the burden of pneumococcal disease among elderly in the Netherlands. PLoS ONE 2018; 13(2): e0192640. https://doi.org/10.1371/journal.pone.0192640 PMid:29425249
48 US Centers for Disease Control. Reasons reported by Medicare beneficiaries for not receiving influenza and pneumococcal vaccinations – United States,1996. Morbidity and Mortality Weekly Report 1999; 48(39): 886-890.
49 Wei W, Findley PA, Sambamoorthi U. Disability and receipt of clinical preventive services among women. Women’s Health Issues 2006; 16(6): 286-296. https://doi.org/10.1016/j.whi.2006.09.002 PMid:17188212
50 Chang YC, Tung HJ, Hsu SW, Chen LS, Kung PT, Huang KH, et al. Use of seasonal influenza vaccination and its associated factors among elderly people with disabilities in Taiwan: a population-based study. PLoS One 2016; 11(6): e0158075. https://doi.org/10.1371/journal.pone.0158075 PMid:27336627
51 Kyriopoulos D, Balasopoulos T, Naoum V, Mavrikou M, Pavi E. Knowledge of vaccination importance among the Greek adult population [e-poster AA29]. Athens: 12th Panhellenic Congress on Management, Economics and Policies in Health. 2016. Available: http://2016.healthpolicycongress.gr/e-poster-files (Accessed 24 January 2019).