Abstract
Objective:
Iso-osmolar Iodixanol is associated with a lower rate of contrast-induced acute kidney injury (CI-AKI) in patients at increased risk compared to low-osmolar contrast media (LOCM). The aim of this study was to assess the financial consequences of CI-AKI risk reduction in patients undergoing coronary angiography (CA) with or without percutaneous coronary intervention (PCI) in German, Italian, Polish and Spanish hospitals.
Methods:
This budget impact analysis (BIA) compared a scenario with iodixanol to a scenario without, where only LOCM were used, in patients at increased risk of CI-AKI over a 3-year horizon. A meta-analysis based on a systematic review observed a lower rate of CI-AKI with iodixanol compared to LOCM (Risk Reduction = 0.46) in patients with underlying impaired renal function (serum creatinine ≥1.6 mg/dl and estimated glomerular filtration rate ≤50 ml/min/1.73 m2). Contrast media and CI-AKI hospitalization costs were included in the analysis and unit costs were obtained from published literature, official sources or, when available, from hospital data. In the absence of country-specific data, resource utilization for a CI-AKI hospitalization was obtained by interviews with local clinicians in each country. The percentage of patients who received iodixanol was assumed to increase over time.
Results:
Based on a percentage of patients at increased risk of CI-AKI equal to 20% in Germany, 24% in Italy, 23% in Poland and 10% in Spain, results showed that the introduction of iodixanol would bring a 3-years cumulative net percentage saving on the total hospital budget of 29%, 34%, 25%, and 33% in the four countries respectively.
Conclusion:
The results of the analysis for the four countries showed that iodixanol use in patients at increased risk of CI-AKI undergoing CA with or without PCI may bring considerable savings on the hospital’s budget, due to the associated reduction in CI-AKI incidence.
Introduction
Intra-arterial contrast media (CM) are used in interventional cardiology to visualize coronary arteries. Although the diagnostic accuracy and tolerance of currently available CM is high, their administration may cause acute kidney injury (AKI) in patients at increased riskCitation1. Moreover, interventional cardiology patients, such as acute myocardial infarction patients, may already be subject to a higher AKI risk due to their underlying conditionCitation1. Contrast-induced AKI (CI-AKI) has acute adverse consequences on the structure and function of the kidney, which, even when reversible, may cause persistent tissue damage in the long-termCitation2. Moreover, severe AKI may lead to irreversible decline in kidney function and, eventually, chronic kidney failureCitation3. The consequences of CI-AKI in terms of co-morbidity and mortality are severe. Epidemiological studies in Europe reported an increase in hospitalization rates and mortality in patients with CI-AKI compared to patients who did not develop CI-AKI following intra-arterial administration of CMCitation1,Citation4,Citation5. Moreover, due to hospitalizations and co-morbidity, CI-AKI severely impacts patients’ quality-of-life, as well as representing a considerable economic burden for the providers at the local and national levelsCitation6.
Given that the number of interventional cardiology procedures has been increasing over the past few years, CI-AKI incidence and its associated clinical and economic burden have become a major concern to clinicians, patients, and budget holders, at both local and regional/national levelsCitation7. While diagnostic accuracy amongst CM may be similar, it is important to identify the CM which offer the best safety profile, particularly in patients at increased risk of developing CI-AKICitation6, i.e., emergency patients for whom the kidney protective preventive protocol cannot be followed and elective patients with pre-existing risk factors such as impaired renal function, diabetes, anemia, and advanced age.
The Nephrotoxic Effects in High-Risk Patients Undergoing Angiography (NEPHRIC) study showed that the use of the iso-osmolar agent (IOCM) iodixanol reduced the incidence of CI-AKI in high risk diabetic patients when compared with iohexolCitation8. Differently from iodixanol, products such as iohexol, iopromide, iomeprol, iobitridol, iopamidol, ioversol, and ioxaglate are known as low-osmolar contrast media (LOCM), defined as such since they have a lower osmolality than the first high-osmolar ionic monomer CM and despite the fact that they have 2–3-times the osmolality of blood. Moreover, meta-analyses of clinical trial data have indicated iodixanol has significantly lower risk of CI-AKI in subjects at increased risk compared to LOCMCitation9,Citation10. In line with such evidence, the European Society of Cardiology (ESC) recommends the use of low or isosmolar CM in patients with moderate-to-severe chronic kidney disease, who are therefore at a higher risk of developing CI-AKICitation11. As reported in the Kidney Disease: Improving Global Outcomes (KDIGO) 2012 clinical practice guideline for the evaluation and management of chronic kidney disease, the use of isosmolar CM can prevent the development of CI-AKI, as well as the associated morbidity and mortality, in patients at increased risk and it should, therefore, be considered over LOCMCitation12.
Following the evidence on a lower CI-AKI risk associated with iodixanol, a budget-impact analysis (BIA) was developed to assess the financial consequences of the use of intra-arterial iodixanol in patients at increased risk of CI-AKI undergoing coronary-angiography (CA) with or without percutaneous coronary intervention (PCI) on the hospital budget in Germany, Italy, Poland, and Spain. The budget-impact model (BIM) compared a scenario with iodixanol, which will substitute a proportion of LOCM administration, to a scenario without iodixanol, where only LOCM (iohexol, iopromide, iomeprol, iobitridol, iopamidol, ioversol and ioxaglate) are used in patients at increased risk of CI-AKI. The study was conducted in 2013 and 2014.
Methods
A BI analysis gives information on whether the new technology is financially sustainable, by estimating the changes in expenditures for a healthcare system, for each period of interest after adoption of the new intervention in the eligible populationCitation13. The current budget impact model was developed in MS Excel™ and was designed to synthesize available country-specific knowledge to estimate the likely financial consequences of iodixanol use for the hospitals in Germany, Italy, Poland, and Spain.
In the absence of country-specific studies reporting the epidemiological and resource use data required to populate the BIM, expert interviews were conducted in each country to derive data on the percentage of patients at increased risk of CI-AKI undergoing CA with or without PCI, the dose (ml) of contrast media used in the procedure, and the resources used during a CI-AKI hospitalization. Resource use included length of stay (ICU, nephrology, cardiology), specialist visits, laboratory tests, dialysis, and diagnostic imaging. A total of 9–12 clinicians, nephrologists, and interventional cardiologists/radiologists were selected in each country on the basis of the relevance and geographical location of the respective hospital, aiming to ensure representativeness at the national level. The selected clinicians completed a questionnaire, which had been previously piloted in each country by local experts. The answers obtained from the questionnaires were described using mean values and were validated by local experts.
Eligible population
The population included in the model was patients at increased risk of developing CI-AKI following CA with or without PCI. The definition of risk used in the base case analysis matched the average patient demographic data reported in the meta-analysis by McCullough and BrownCitation10. That is, patients with underlying impaired renal function, described as serum creatinine ≥1.6 mg/dl (141.44 µmol/L) and glomerular filtration rate ≤ 50 ml/min/1.73 m2. The experts who participated at the Italian advisory board (AB) suggested that emergency patients (for example patients with an acute myocardial infarction needing an emergency PCI) for whom the CI-AKI preventive protocol cannot be followed, could also be considered among the CI-AKI increased risk group in addition to patients with underlying impaired renal function. Hence, the emergency patients’ sub-population was added in a scenario analysis. Given that Italy was the only country for which experts at the AB asked to obtain the percentage of emergency patients in the interviews performed, the Italian percentage was used to run the scenario analysis in all four countries assessed ().
Table 1. Epidemiological data to derive the eligible number of patients at each year of the analysis.
In all countries the patient flow () was built assuming a starting number of 1000 patients undergoing CA with or without PCI at the first year of the analysis. The proportion of patients at increased risk of CI-AKI undergoing CA with or without PCI was obtained from the interviews with the clinicians. Finally, a positive percentage growth was applied to the number of patients at the first year to derive the number of eligible patients at second and third year of the analysis. A positive percentage growth was chosen to represent the increasing trend in interventional cardiology procedures and was also derived from the interviews with experts cardiologists in the four countries considered.
Model structure and intervention mix
The current BIA compared the starting scenario, where all eligible patients were administered a mix of LOCM based on country-specific patient shares, to a future scenario, where iodixanol was used in a gradually increasing share of eligible patients replacing the use of LOCM. The total cost associated to each scenario was calculated summing up contrast media and CI-AKI management cost accrued during inpatient hospital stay. The time horizon of the analysis was 3 years. This time horizon was chosen as it is likely to be of most relevance to the hospital budget holder.
The analysis included all LOCM commonly used in interventional cardiology, namely iohexol, iopromide, iomeprol, iobitridol, iopamidol, ioversol and ioxaglate. Country-specific and constant patient shares over time were used to define the LOCM mix in the starting scenario for each countryCitation14 ().
Table 2. Market shares in the scenario without and the scenario with iodixanol.
Iodixanol is introduced in the future scenario replacing LOCM with an increasing proportion. A simple linear increase of iodixanol use over time was assumed to measure the financial impact on the hospital budget with use in approximately one-third, two-thirds, and the total population at increased risk of CI-AKI at first, second, and third year of the analysis, respectively. Please note that iodixanol is available in the different countries at the moment and, as such, the analyses are purely hypothetical.
Clinical data
The current BIA focused on the outcome of CA with or without PCI enhanced by CM, merely in terms of CI-AKI incidence. The incidence of CI-AKI in patients at increased risk was obtained from a published meta-analysis based on a well-specified systematic review, where CI-AKI was defined as an increase in baseline serum creatinine ≥ 0.5 mg/dl (44.2 µmol/L), or an increase in serum creatinine of at least 25%, measured up to 3 days following contrast exposureCitation10. McCullough and BrownCitation10 reported an incidence of CI-AKI equal to 18.54% in patients at increased risk who underwent the procedure with LOCM (iohexol, iomeprol, iopamidol, iopromide, ioversol and ioxaglate) and a CI-AKI relative risk of 0.46 for iodixanol vs LOCM. Given that nearly all LOCM available were included in the McCullough and Brown meta-analysis, the derived CI-AKI risk was applied to all LOCM included in the current analysis. The CI-AKI incidence rate from McCullough and BrownCitation10 was also used in the scenario analysis, despite the different definition of CI-AKI increased risk which included also emergency patients. However, a study in emergency patients from Manari et al.Citation15 reported a similar CI-AKI incidence rate equal to 18.1%. The meta-analysis by McCullough and BrownCitation10 was selected due to its robust design, results from intra-arterial administration consistent with a PCI population, clearly defined inclusion criteria of risk patients and with a primary endpoint of CI-AKI. The results of a study by Dong et al.Citation9, another widely cited systematic review, were in line with McCullough and Brown’s study.
Resource use and costs
In the current BIA we considered CM acquisition costs and CI-AKI hospitalizations costs. The dose of CM used in CA with or without PCI was reported in terms of milliliters of product () and was obtained from questionnaires distributed to clinicians in each country, in order to derive data accurately reflecting the standard of treatment at the local level. The average dose (ml) of CM varied across the four countries, showing differences in standard of care: Germany and Italy administer the highest doses, with 200 ml and 188 ml, respectively, followed by Spain with 145 ml, and Poland, where, on average, clinicians administer a CM dose of 95 ml.
Table 3. Resource use in each country: mean values calculated from the results of experts’ interviews.
The current BIA considered only hospital resources used for the inpatient treatment of CI-AKI. Experts interviewed in all four countries were asked to quantify resource use during CI-AKI hospitalization (). Differently from the other countries, the BIA conducted for Italy differentiated in resources used to treat CI-AKI at the three levels of severity, as defined by the KDIGO guidelines on AKICitation16. This approach was suggested by local experts involved in the validation of the questionnaire as a way to improve accuracy in resource use data collection.
All costs were updated at current price level using country-specific inflation index and were reported in Euros (1 PLN = €0.243 at March 2015) to allow comparisons between countries. CM prices () are negotiated between manufacturers and hospitals based on a tendering process in all four countries assessed. Given that prices to hospitals are negotiated between manufacturers and hospitals/regions in all four countries considered, we used confidential rebate prices instead of list prices to better reflect the real worldCitation14,Citation17–19. For Italy, we used prices coming from hospital rebates in the Tuscany region, which could be accessed through one of the experts involved in the country’s advisory boardCitation19.
Table 4. Unit costs per country.
Total hospitalization costs were obtained using a micro-costing approach with an attempt to represent the hospital perspective. Where available, peer-reviewed hospital cost studiesCitation20 were used to obtain country-specific hospital unit costs to populate the model. Alternatively, national tariffs and payment rates from official databases were used as a proxyCitation21–31 (). All costs and respective sources were validated at each respective country’s advisory board.
Analysis
In base case analysis we calculated the difference between the total cost accrued in the scenario with iodixanol and in the scenario without iodixanol. The budget impact was calculated at each year of the analysis and cumulative over the 3 years. In addition to base case analysis, we conducted one scenario analysis, to study how results would change if emergency patients were included in the definition of CI-AKI increased risk, as is the case in the Italian scenario. Given that the percentage of emergency patients was not collected for Germany, Poland, and Spain, the Italian value (26% emergency patients) was added to the base case percentage of patients at increased risk of CI-AKI in Germany, Poland, and Spain.
One-way sensitivity analyses (OWSA) were performed to assess how variations in model parameters impact base case results. Model parameters were varied within a pre-defined range of ±20% and results were presented through a Tornado diagram, which allows simultaneous visualization of results in the 10 most influent parameters/assumptions on base-case results.
Results
The results from the questionnaires were aggregated calculating the arithmetic mean between the answers given by experts in each country to obtain epidemiological () and resource use () data to populate the models. Total CI-AKI hospitalization costs were obtained adjusting local unit costs by resource use (). Ward stay (including ICU) represented the highest cost per patient in CI-AKI hospitalization across all countries assessed and ranged from €1123 (PLN 2648) in Poland to €3869 in Spain. Within ward stay, the cardiology ward represented the highest cost in all countries but Poland, where a higher LOS in nephrology drove larger costs in this ward. Pharmaceutical costs are highest in Italy, despite a lower CM dose than in Germany. Total Iodixanol spending is lowest in Poland, due to the lower CM dose than in the other countries, whereas LOCM cost is lowest in Germany, despite having the highest reported CM dose ( and ).
Table 5. Total and breakdown of cost (Euros) per CI-AKI hospitalization per patient in each country (local unit cost adjusted by resource use).
Based on a percentage of patients at increased risk of CI-AKI equal to 20% in Germany, 24% in Italy, 23% in Poland and 10% in Spain, and an estimated cost per CI-AKI episode per patient of €2368 in Germany, €2817 in Italy, €1123 (PLN 4629) in Poland, and €4104 in Spain, the introduction of iodixanol in patients at increased risk of CI-AKI undergoing CA with or without PCI brought overall savings on the hospital budget in all four countries (). Overall, the estimated number of patients entering the analysis at every year was similar between the countries considered, with the exception of Spain due to the lower percentage of patients at increased risk of CI-AKI. CI-AKI hospitalization cost accounted for over 90% of the total cost in all countries except for Poland, where it accounted for ∼73%. The percentage reduction in total cost in the scenario with iodixanol compared to the scenario without iodixanol increased over time and was broadly similar between the four countries, varying slightly between 25% (Poland) and 34% (Italy) (). The reduction in total hospital cost associated to the scenario with iodixanol was mainly related to the increase in iodixanol share and only partially related to population increase over the years of the analysis.
Table 6. Base case analysis results: impact on hospital budget following the introduction of iodixanol.
Scenario analysis results showed that, after the inclusion of emergency patients among the population at increased risk of CI-AKI, the saving as an absolute number increased; however, the percentage reduction remained constant in all four countries ().
Table 7. Scenario analysis results: impact on hospital budget following the introduction of iodixanol, assuming emergency patients are included within the definition of CI-AKI increased risk.
OWSA showed robustness of base case results in all four countries. The most influential parameters on the 3-years cumulative budget impact results were iodixanol vs LOCM RR of CI-AKI, CI-AKI incidence in LOCM, and LOS in cardiology ward (LOS in nephrology ward for Poland); however, the savings from the introduction of iodixanol were maintained across variations in parameters for all four countries considered (). Given the important impact of CI-AKI relative risk of iodixanol vs LOCM, we performed an additional analysis to evaluate at which level of relative risk the use of iodixanol would result in a higher total cost for the hospital. Results showed that this would only occur when the difference in CI-AKI incidence between iodixanol and LOCM is very small, with a CI-AKI relative risk of ∼0.96 for Germany, 0.88 for Poland, and 0.98 for Spain and Italy.
Figure 1. Tornado diagrams presenting OWSA on the 3-years cumulative budget impact for the 10 most influent variables. Only eight variables are presented for Spain as all others did not have any impact on base case result.
Discussion
The aim of the current analysis was to measure the financial consequence of the use of iodixanol in CI-AKI increased risk patients undergoing CA with or without PCI on the hospital budget in four European countries; Germany, Italy, Poland, and Spain, considering contrast media and CI-AKI hospitalization costs. This study showed that important clinical and economic benefit can result from the administration of iodixanol in patients at increased risk of CI-AKI, given the observed reduction in CI-AKI events compared to LOCM. The results of the analysis showed that iodixanol used in substitution for LOCM in patients at increased risk of CI-AKI undergoing CA with or without PCI would be associated with a reduction in CI-AKI events, which in turn would bring important savings for hospitals’ budgets in the four countries assessed. Most importantly, the introduction of iodixanol was associated with a lower total cost in all countries assessed despite differences in the percentage of patients at increased risk of CI-AKI, resource use, and cost data obtained from the interviews with local experts. Such differences may reflect the different standard practice in the treatment of CI-AKI, as well as experts’ different perception of ‘increased risk of CI-AKI’, across the four countries assessed. The results of the current study are in line with the KDIGO clinical practice guideline which, despite the higher acquisition cost compared to LOCM, recommends the use of isosmolar CM because of its beneficial impact in terms of avoided morbidity and mortality in patients at increased riskCitation12. Finally, scenario analysis showed that results were consistent when a different definition of patients at increased risk of CI-AKI was considered. Further research could be conducted to assess the budget impact of iodixanol use in other patients groups and indications. An example is transcatheter aortic valve implantation (TAVI) patients, who are at high risk of CI-AKI given their advanced age and overall health conditionCitation32.
Local clinicians were interviewed to obtain a representative quantification of the average resource use per CI-AKI hospitalization in each country. Results of the interviews showed that there is some homogeneity in CI-AKI management across the four countries. First of all in most patients CI-AKI is diagnosed before they are discharged. Second, most patients are kept in the cardiology ward and receive nephrologists’ consultations during hospital stay, with the exception of Poland, where the proportion of patients is equally distributed between the cardiology and nephrology ward. Third, average LOS is similar across all countries ranging from 4–6 days. Fourth, hemodialysis is more commonly performed compared to hemofiltration in all countries. Lastly, nearly all the same types of laboratory and diagnostic imaging tests were mentioned by the experts in all countries, indicating that similar standard clinical practices are followed.
In interpreting the results of the current analysis, it is important to consider the country-specific financing system, i.e., diagnosis related group (DRG) tariffs vs fee-for-service. In the four countries assessed, DRGs are used as the basis for hospital payment rates. Briefly, this means that a single DRG rate can be applied to each discharge, independently of the resources used during hospitalization and this is true in both DRG-based case payment systems (Germany, Poland, and Spain) and in DRG-based budget allocation systems (Italy)Citation33. Hence, hospitals have an incentive to reduce costs per treated patients within a single admission or for which a single payment rate is applied, e.g., re-hospitalizations within 30 days from initial discharge. In such context the current BIM is relevant in informing hospital budget holders that using a less expensive CM to make direct savings is not necessarily the best option if complications are taken into account. However, cost reductions may be less in countries where hospitals are paid through fee-for-service payment systemsCitation33.
To our knowledge, this was the first attempt to estimate the financial consequences of the use of iodixanol in patients at increased risk of CI-AKI on the hospital budget in terms of contrast media acquisition cost and hospital cost associated with the treatment CI-AKI. In this respect, it is important to stress that, although the current analysis was designed to take the hospital perspective, i.e. taking into account only costs entirely borne by the hospital, it may hold value in informing regional/national budget holders of both size and direction of the likely impact on their budget for two reasons: first of all, savings on the budget of an inner organization are always likely to reverberate on the budget of an outer organization within publicly funded healthcare service. That is, hospitals budgets come from the local/regional or national budgets and DRG payments rates are built based on actual hospital costs, hence lower costs means also lower DRG tariffs in the long-termCitation33. Second, due to the lack of publicly available hospital costs, the present study was mainly populated using reimbursement tariffs as a proxy, thus meaning that if national level epidemiological data are used, results may be interpreted in terms of financial impact on the national healthcare budget of the country considered.
The current budget impact model presents some limitations. First of all, a generally accepted definition of patients at increased risk of CI-AKI is missing and the percentage of patients at increased risk of CI-AKI could not be obtained from official databases or observational studies (not available); however, it represents the perception of CI-AKI increased risk by the interviewed clinicians; second, the same risk of CI-AKI, obtained from the meta-analysis by McCullough and BrownCitation10, was applied to all LOCM in our study. McCullough and BrownCitation10 calculated the risk of CI-AKI based on clinical studies on all LOCM included in our model, at the exception of iobitridol. To overcome such a limitation we ran a scenario analysis to test the sensitivity of results for varying levels of CI-AKI relative risk between LOCM and iodixanol. The findings show that iodixanol would stop being cost saving only at very high CI-AKI relative risk (≥0.88), as presented in the results section of this manuscript; third, given that the hospitalization costs are the main drivers of the BI results, an important flaw refers to the difficulty to capture only costs which are entirely borne by the hospitals, due to the complexity of the financing system. Furthermore, the lack of publicly available hospital costs meant that official national tariffs had to be used as a proxy.
Recognizing methodological limitations, the current budget impact analyses provide important information about the financial sustainability of iodixanol in four European countries. The results of this analysis suggests that the value of iodixanol in terms of a lower rate of CI-AKI may be beneficial to both patients, thanks to fewer adverse events and as such quality-of-life, and hospitals, as well as the healthcare system as a whole, due to a reduction in the number of CI-AKI related hospitalizations and associated savings.
Transparency
Declaration of funding
GE Healthcare provided funding for this manuscript.
Declaration of financial/other relationships
GE Healthcare contracted IMS Health to develop the model and conduct the present study in Germany, Italy, Poland, and Spain. ML and MDF are employees of IMS Health. CR, PJW, RW, and FH received a consulting fee of GE Healthcare. JME peer reviewers on this manuscript have no relevant financial or other relationships to disclose.
Acknowledgments
The authors of this paper acknowledge the contribution given by IMS Health team members Stijn Vandekerckhove, Roger-Axel Greiner and Carmen Barrull in the adaptation of the model to local setting, by GE Healthcare team members who supported the development of the project, by the Key Opinion Leaders involved in the advisory boards that took place in each country (Spain: Dr Angel L.M. de Francisco, Dr José María Hernández, Dr Fina Mauri, Dr Francisco Picó-Aracil, Dr Eduardo Pinar, Dr Rafael Ruiz-Salmerón. Germany: Prof Bernd Hohenstein, Prof Peter Grob, Prof Dr Matthias Girndt, Dr Klaus Thürmel, Dr Frank Burger, PD, Dr Johannes Rieber, Dr Michaela Klauck, Dr Ji-Hyun You, Dr med. Frank van Buuren. Italy: Dr Antonio Manari, Dr Marcello Pani. Poland: Dr Sławomir Dobrzycki, Dr Robert Juszkat, Dr Jacek Kubica, Dr Maciej Lesiak, Dr Michał Nowicki, Dr Andrzej Ochała, Dr Przemyslaw Rutkowski, Dr Piotr Waciń ski, Dr Adam Zapaśnik, Dr Janusz Kochman, Dr Aleksander Falkowski, Dr Rafał Donderski).
References
- Kooiman J, Le Haen PA, Gezgin G, et al. Contrast-induced acute kidney injury and clinical outcomes after intra-arterial and intravenous contrast administration: risk comparison adjusted for patient characteristics by design. Am Heart J 2013;165:793-9
- Fliser D, Laville M, Covic A, et al. A European Renal Best Practice (ERBP) position statement on the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines on Acute Kidney Injury: Part 1: definitions, conservative management and contrast-induced nephropathy. Nephrol Dial Transplant 2012;27:4263-72
- Chawla LS, Amdur RL, Amodeo S, et al. The severity of acute kidney injury predicts progression to chronic kidney disease. Kidney Int 2011;79:1361-9
- Tehrani S, Laing C, Yellon DM, et al. Contrast-induced acute kidney injury following PCI. Eur J Clin Invest 2013;43:483-90
- Valette X, Parienti JJ, Plaud B, et al. Incidence, morbidity, and mortality of contrast-induced acute kidney injury in a surgical intensive care unit: a prospective cohort study. J Crit Care 2012;27:322.e1-5
- Weisbord SD, Palevsky PM. Contrast-induced acute kidney injury: short- and long-term implications. Semin Nephrol 2011;31:300-9
- National Institute for Health and Care Excellence. Acute kidney injury: prevention, detection and management of acute kidney injury up to the point of renal replacement therapy. Clinical guideline 169. London, UK: National Institute for Health and Care Excellence; 28 August 2013. Available at: nice.org.uk/guidance/cg169 [Accessed March 2015]
- Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxicity in high-risk patients study of iso-osmolar and low-osmolar non-ionic contrast media study investigators. Nephrotoxic effects in high-risk patients undergoing angiography. N Engl J Med 2003;348:491-9
- Dong M, Jiao Z, Liu T, et al. Effect of administration route on the renal safety of contrast agents: a meta-analysis of randomized controlled trials. J Nephrol 2012;25:290-301
- McCullough PA, Brown JR. Effects of intra-arterial and intravenous iso-osmolar contrast medium (Iodixanol) on the risk of contrast-induced acute kidney injury: a meta-analysis. Cardiorenal Med 2011;1:220-34
- Windecker S, Kolh P, Alfonso F, et al. ESC/EACTS Guidelines on Myocardial Revascularisation. Eur Heart J 2014;35:2541-619
- KDIGO. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013;3:1-150
- Sullivan SD, Mauskopf JA, Federico Augustovski F, et al. Budget impact analysis—Principles of good practice: report of the ISPOR 2012 Budget Impact Analysis Good Practice II Task Force. Value in Health 2014;7:5–14
- GE Healthcare. Drug prices & market shares. 2013. [Confidential internal material]
- Manari A, Magnavacchi P, Puggioni E, et al. Acute kidney injury after primary angioplasty: effect of different hydration treatments. J Cardiovasc Med 2014;15:60-7
- Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Inter Suppl. 2012;2:1–138
- Statistisches Bundesamt Wiesbaden, Reihe 12, Fachserien 6.2, 6.3, 2011
- GE Healthcare. Drug prices. 2014. [Confidential internal materials]
- Listino vigente con i prezzi unitari (IVA esclusa) delle gare ospedaliere della regione Toscana. Confidential document.
- Colombo GL, Lundkvist J, Carugg M, et al. Analisi dei costi in pazienti ad alto rischio di nefropatia indotta da mezzo di contrasto: i risultati per l’Italia dello studio NEPHRIC. PharmacoEconomics - Italian Research Articles 2013;7:145–54
- DKG NT Band I, 2007, 31. edition, German hospital association [Deutsche Krankenhausgesellschaft] - regular tariff. Stuttgart: Kohlhammer Verlag, 2007
- Lauer-Fischer Taxe, Portal 2014. Available at: http://www.lauer-fischer.de/lf/Seiten/Lauer-Taxe-online/Lauer-Taxe-online-EN-demo.aspx [Accessed December 2014]
- Database e-salud. 2013. Available at: http://www.oblikue.com/bddcostes/ [Accessed December 2014]
- Ministerio de Sanidad, Política Social e Igualdad. Instituto de Información Sanitaria, Registro de altas - CMBD 2011. Available at: http://www.msssi.gob.es/estadEstudios/estadisticas/cmbdhome.htm [Accessed November 2014]
- Szpitalzdrowia 2014. Available at: http://www.szpitalzdrowia.pl/wp-content/uploads/2013/08/CENNIK-OSOBODNIA-POBYTU-W-ODDZIALE_obowiazuje-od-1-sierpnia-2013.pdf. [Accessed January 2015]
- WIM 2014. Available at: http://www.wim.mil.pl/images/Pacjent/cennik%20us%B3ug%20medycznych.pdf. [Accessed December 2014]
- USK Bialystok 2014. Available at: http://www.usk.bialystok.pl/diag_kl/cennik.htm. [Accessed December 2014]
- Luxmedlublin 2014. Available at: http://www.luxmedlublin.pl/. [Accessed January 2015]
- Hemiled 2014. Available at: http://www.helimed.pl/tomografia_komputerowa/tomografia_komputerowa_cennik.ht. [Accessed December 2014]
- Hemiled 2014. Available at: http://www.avi.med.pl/rezonans_magnetyczny/ce. [Accessed December 2014]
- Ministero della Salute. Prestazioni di Assistenza Specialistica Ambulatoriale. Ministero della Salute, Rome, Italy, January 2013; Supplemento ordinario n. 8 alla. Gazzetta Ufficiale; Serie generale n. 23
- Yamamoto M, Hayashida K, Mouillet G, et al. Renal function-based contrast dosing predicts acute kidney injury following transcatheter aortic valve implantation. JACC Cardiovasc Interv 2013;6:479-86
- Busse R, Geissler A, Quentin W, et al, eds. Diagnosis-related groups in Europe. Moving towards transparency, efficiency and quality in hospitals. European Observatory on Health Systems and Policies Series. Mc Graw Hill, Open University Press, Berkshire, England 2011