- Research article
- Open Access
- Open Peer Review
This article has Open Peer Review reports available.
Impact of availability of guidelines and active surveillance in reducing the incidence of ventilator-associated pneumonia in Europe and worldwide
© Kaier et al.; licensee BioMed Central Ltd. 2014
Received: 26 July 2013
Accepted: 8 April 2014
Published: 12 April 2014
To analyse whether the availability of written standards for management of mechanically ventilated patients and/or the existence of a surveillance system for cases of ventilation-associated pneumonia (VAP) are positively associated with compliance with 6 well-established VAP prevention measures.
Ecological study based on responses to an online-questionnaire completed by 1730 critical care physicians. Replies were received from 77 different countries, of which the majority, i.e. 1351, came from 36 European countries.
On a cross-country level, compliance with VAP prevention measures is higher in countries with a large number of prevention standards and/or VAP surveillance systems in place at ICU level., Likewise, implementation of standards and VAP surveillance systems has a significant impact on self-reported total compliance with VAP prevention measures (both p < 0.001). Moreover, predictions of overall prevention measure compliance show the effect size of the availability of written standards and existence of surveillance system. For instance, a female physician with 10 years of experience in critical care working in a 15-bed ICU in France has a predicted baseline level of VAP prevention measure compliance of 63 per cent. This baseline level increases by 9.5 percentage points (p < 0.001) if a written clinical VAP prevention standard is available in the ICU, and by another 4 percentage points (p < 0.001) if complemented by a VAP surveillance system.
The existence of written standards for management of mechanically ventilated patients in an ICU and the availability of VAP surveillance systems have shown to be positively associated with compliance with VAP prevention measures and should be fostered on a policy level.
Healthcare-associated infections (HAIs) are considered to be a major risk for hospitalised patients and the cause of substantial increases in morbidity, mortality and costs in European Union (EU) member states. Approximately 7 percent of hospitalized patients acquire an HAI while receiving treatment for medical or surgical conditions , and it is estimated that each year approximately 37,000 lives are lost to HAI in the EU alone. Healthcare-associated infections incur an estimated Euro 7 billion in excess healthcare costs per annum in the EU, caused mainly by increased length of hospital stay . HAIs are associated with a variety of causes, including but not limited to use of medical devices such as catheters and ventilators, complications following surgical procedures, transmission of pathogens or antibiotic overuse [3, 4]. HAIs are often difficult to treat due to antimicrobial resistance (AMR) of the microorganisms causing them . There is a public health interest in preventing HAIs, as laid out in the European Council recommendation of 9th June 2009 in which HAI prevention measures were adopted as part of patient safety programs and quality improvement initiatives [6, 7]. National HAI-prevention programs include establishment of surveillance systems, publication of guidelines and measuring structure and process indicators. Furthermore, some European countries have established public reporting of data on HAI from individual hospitals [8, 9].
Pneumonia was the HAI most frequently reported in the ECDC pilot point prevalence survey , and is most common in the intensive care unit (ICU) [10, 11], where a relevant proportion of patients receive mechanical ventilation. Many studies provide evidence for the preventive effectiveness of single interventions, leaving the decision-maker with the complex task of selecting the best one [12–16]. Recently, there has been dramatic success in improving the quality of patient care by focusing on the implementation of an entire group or “bundle” of evidence-based preventive practices [17–19]. These bundle approaches achieve better outcomes than individual implementation of single procedures [20–24], and, from the hospital perspective, have shown to be cost-effective [25, 26].
The infection prevention and control measures that have been applied in hospitals to reduce ventilator-associated pneumonia (VAP) vary widely, both within and between different countries . A harmonized approach, based on the application of core strategies developed through an evidence-based approach and comprising specific strategies which relate to local characteristics and context e.g., the affected patient case-mix, should result in a more comparable situation. However, consensus is missing on the most effective infection control interventions or the best combination of interventions to reduce VAP in hospitalized patients. Therefore, we performed a survey to define the level of heterogeneity and analyse related outcomes. In detail, we used the information collected in a questionnaire completed by 1730 ICU physicians across Europe and around the world to analyze whether the availability of written standards for the management of mechanically ventilated patients and/or the existence of a VAP surveillance system on ICU-level are positively associated with compliance with a number of well-established VAP prevention measures.
Non-representative country averages for countries with >20 responses
Number of responses
Number of pseudo-ICUs
Mean years of experience in critical care
Proportion female sex
Number of beds in ICU
Availability of VAP prevention standards
Existence of VAP surveillance system
VAP measure 1
VAP measure 2
VAP measure 3
VAP measure 4
VAP measure 5
VAP measure 6
Sum of VAP measures 1-6
Although there is no universally accepted gold standard for prevention of VAP, a recent study defined a European care bundle for prevention of VAP and ranked VAP prevention measures by combining criteria such as the strength of the supporting evidence, ease of implementation and expected impact on VAP incidence . The top five clinical interventions of this ranking were included in our questionnaire (VAP prevention measure 2–6). As a control, the most commonly recommended clinical practice of head of bed elevation was included in the survey and analyzed as VAP prevention measure 1. Accordingly, self-reported compliance with the target VAP prevention measures were interpreted as compliance with bundle-like VAP prevention measures under routine conditions.
The statistical analysis consisted of three steps. In a first step, country-specific averages of stated compliance with specific VAP prevention measures univariately regressed against the country-average responses to the questions on whether there were written clinical guidelines in place on ICU level for prevention of VAP (and whether there were VAP surveillance systems in place). The results provide a first insight into the relationship between described variables on a cross-country level. Next, within-country averages of stated compliance with the VAP prevention measures were calculated separately for physicians stating whether their ICU had written VAP-standards or not (and whether they had VAP surveillance systems in place or not). Thus, the evidence from these within-country differences in average compliance with the VAP prevention measures was summarized by a p-value from a paired Student’s t-test. In a further step, we endeavoured to utilize the information on inter-ICU differences, i.e. on whether associations exist at ICU-level within each country. Unfortunately, the ICU of each participant is not known. Because our main outcome was defined at ICU level – i.e. compliance with 6 specific measures, we were forced to define pseudo-ICUs by analysing patterns in the ICU characteristics reported by the participants (country of abode, ICU type, number of beds in ICU and number of beds in hospital) and then grouping participants with similar patterns into pseudo-ICUs. This was done in a rather liberal manner to ensure that each existing ICU was covered by a pseudo-ICU, at the same time allowing for pseudo-ICUs to cover several responses. For ICU type and number of beds in hospital only three answers were possible (ICU type: medical, surgical, mixed; number of beds in hospital: < 300, 300–1000, > 1000) while number of beds in an ICU was a continuous variable. The number of ICUs we were able to define this way in the different countries is shown in Table 1. Within each pseudo-ICU we have some variation in the individual responses, which both reflects the flaws in the pseudo-ICUs and the differences in the individual responses within an ICU. We therefore decided to perform an analysis at the individual level, taking however both country and pseudo-ICU levels into account to avoid an overoptimistic assessment of the statistical significance since we had ignored the high correlations between the outcomes within each ICU. Moreover, using pseudo ICUs instead of the true ICUs results in more valid p-values here because possible and to some extent unknown clustering is taken into account. We used linear regression/logistic regression models with the covariates of interest, adjusting for country (as a categorical covariate) as well as number of beds, gender and experience as individual measurements, and took the clustering within pseudo ICUs into account by using robust standard errors (application of the cluster option in Stata 12). Using pseudo ICUs instead of ICUs is a valid approach here because the central assumption of independence of the outcomes between clusters is still valid, even if the clusters are bigger than necessary. As covariates of interest we included presence of written clinical standards on ICU level and presence of VAP surveillance systems.
Standard existence and compliance with VAP prevention measures
As shown in Additional file 1: Figure S1 (available as supplemental material), the results displayed by individual prevention measures provide mixed results. VAP prevention measure 1 - head of bed elevation - is commonly recommended clinical practice with high rates of compliance; however, when looking at the between-country or within-country averages there does not seem to be an obvious connection with the presence of VAP prevention standards. Regarding VAP prevention measure 2 and 3, which refer to daily sedation vacation and weaning protocol and oral care with chlorhexidine, there seems to be a connection between the respective prevention measure and the existence of VAP prevention standards when regarding the between- country and within- country averages. Regarding VAP prevention measure 4 and 5, which refer to no ventilator circuit change unless indicated and cuff pressure control at least every 24 hrs, the country-averages show no clear connection. VAP prevention measure 6, which represents strict hand hygiene using alcohol, especially before managing the airways, shows quite a strong association when looking at the within-country averages, but absolutely no association when looking at the between-country averages.
Existence of VAP surveillance system and compliance with VAP prevention measures
Results of statistical analysis at the individual level
Results of statistical analyses at the ICU level
Logistic regression VAP measure 1
Logistic regression VAP measure 2
Logistic regression VAP measure 3
Logistic regression VAP measure 4
Logistic regression VAP measure 5
Logistic regression VAP measure 6
Linear regression VAP measures 1-6
Availability of VAP guidelines on ICU level
Existence of VAP surveillance system on ICU level
Years of experience in critical care
Number of beds in ICU
Our results indicate that the availability of written guidance documents (we do not know whether they were really guidelines or internal guidance documents) to prevent VAP in ICU patients is significantly associated with compliance with the prevention measures. A number of interventional studies exist that analyse adherence with all elements of previously defined ventilator bundles [19, 25, 26, 34, 35]. In a comparative approach, Bouadma et al.  analysed the preventive impact of increased compliance with backrest elevation, tracheal cuff pressure maintenance, orogastric tube use, gastric overdistension avoidance, good oral hygiene and nonessential tracheal suction elimination in a 20-bed medical ICU in a teaching hospital in France . The authors define a composite score of compliance with the different measures (range, 0–6), and show that after implementation of the bundle in their ICU, the score significantly increased over time, while the VAP prevalence rate decreased . Although the present analysis also uses a score of compliance with prevention measures, the focus however is on the question of why compliance scores differ across ICUs in the absence of specific interventions. Interestingly, our results also point out the positive impact of surveillance systems on compliance with VAP prevention measures. Although the cause-and-effect chain between surveillance and prevention measure compliance is still unclear, the efficacy of surveillance systems in the prevention of hospital acquired infections has been shown previously [36–39]. Moreover, the results also show the heterogeneity among European and non-European countries in the level of compliance with VAP prevention measures. According to the evidence presented here, this heterogeneity may to some degree be explained by the heterogeneity in the availability of standards and the existence of surveillance system. The ICU-specific cause-and-effect relationship between availability of standards, and/or the existence of surveillance system and compliance with VAP prevention measures, however, is still unclear. Hence, we cannot exclude that the availability of standards (and/or surveillance system existence) might be a result rather than a cause of a high level of awareness of VAP, which, in turn, results in a high level of compliance with VAP prevention measures. We may only conclude that on average, ICUs where standards are available and surveillance systems are in place report a significantly higher level of compliance with VAP prevention measures irrespective of national compliance levels.
It should be noted that there are a number of limitations to the work we present that must be taken into account. Firstly, to preserve the respondents’ anonymity, the online questionnaire did not include questions allowing for identification of the ICU . Accordingly, we were faced with the problem that the participant’s identity was unknown. Secondly, the survey did not include randomised sampling, meaning that some categories of ICU physician might have been overrepresented and that the country-averages shown in Table 1 cannot be generalized. Thirdly self-reported compliance might also have been subject to overreporting. Finally, we do not know what type of document the respondents were referring to when confirming the availability of standards on the ICU level. Overall, there was no possibility to validate any of the 1730 responses.
This study shows wide variability in compliance with VAP-preventive measures across ICUs in Europe. However, two things seem to be of special interest for improvement of compliance: The presence of written standards for management of mechanically ventilated patients and existence of an established VAP surveillance system. These two basic IPC measures should be fostered on a policy level.
We thank Deborah Lawrie for helpful comments on the manuscript. The article processing charge was funded by the German Research Foundation (DFG) and the Albert Ludwigs University Freiburg in the funding programme Open Access Publishing
- Zarb P, Coignard B, Griskeviciene J, Muller A, Vankerckhoven V, Weist K, Goossens M, Vaerenberg S, Hopkins S, Catry B, Monnet D, Goossens H, Suetens C, National Contact Points for the ECDC pilot point prevalence survey; Hospital Contact Points for the ECDC pilot point prevalence survey: The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial use. Euro Surveill. 2012, 17 (46): Available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20316 Google Scholar
- European Centre for Disease Prevention and Control: Annual Epidemiological Report on Communicable Diseases in Europe 2008. 2008, Stockholm: European Centre for Disease Prevention and Control, Ref Type: ReportGoogle Scholar
- van der Kooi TI, de Boer AS, Manniën J, Wille JC, Beaumont MT, Mooi BW, van den Hof S: Incidence and risk factors of device-associated infections and associated mortality at the intensive care in the Dutch surveillance system. Intensive Care Med. 2007, 33: 271-278. 10.1007/s00134-006-0464-3.View ArticlePubMedGoogle Scholar
- Calfee DP: Crisis in hospital-acquired, healthcare-associated infections. Annu Rev Med. 2012, 63: 359-371. 10.1146/annurev-med-081210-144458.View ArticlePubMedGoogle Scholar
- Theuretzbacher U: Global antibacterial resistance: the never-ending story. J Glob Antimicrob Resist. 2013, 1: 63-69. 10.1016/j.jgar.2013.03.010.View ArticleGoogle Scholar
- McGill L: Patient safety: a European Union priority. Clin Med. 2009, 9: 136-139. 10.7861/clinmedicine.9-2-136.View ArticleGoogle Scholar
- The Council of the European Union: Council recommendation on patient safety, including the prevention and control of healthcare associated infections. Off J Eur Union. 2009, C151: 1-6.Google Scholar
- Haustein T, Gastmeier P, Holmes A, Lucet JC, Shannon RP, Pittet D, Harbarth S: Use of benchmarking and public reporting for infection control in four high-income countries. Lancet Infect Dis. 2011, 11: 471-481. 10.1016/S1473-3099(10)70315-7.View ArticlePubMedGoogle Scholar
- Martin M, Zingg W, Hansen S, Gastmeier P, Wu AW, Pittet D, Dettenkofer M, PROHIBIT study group: Public reporting of healthcare-associated infection data in Europe. What are the views of infection prevention opinion leaders?. J Hosp Infect. 2013, 83: 94-98. 10.1016/j.jhin.2012.10.010.View ArticlePubMedGoogle Scholar
- Lambert ML, Suetens C, Savey A, Palomar M, Hiesmayr M, Morales I, Agodi A, Frank U, Mertens K, Schumacher M, Wolkewitz M: Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study. Lancet Infect Dis. 2011, 11: 30-38. 10.1016/S1473-3099(10)70258-9.View ArticlePubMedGoogle Scholar
- Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, Moreno R, Lipman J, Gomersall C, Sakr Y, Reinhart K, EPIC II Group of Investigators: International study of the prevalence and outcomes of infection in intensive care units. JAMA. 2009, 302: 2323-2329. 10.1001/jama.2009.1754.View ArticlePubMedGoogle Scholar
- Dezfulian C, Shojania K, Collard HR, Kim HM, Matthay MA, Saint S: Subglottic secretion drainage for preventing ventilator-associated pneumonia: a meta-analysis. Am J Med. 2005, 118: 11-18. 10.1016/j.amjmed.2004.07.051.View ArticlePubMedGoogle Scholar
- Labeau SO, Van de Vyver K, Brusselaers N, Vogelaers D, Blot SI: Prevention of ventilator-associated pneumonia with oral antiseptics: a systematic review and meta-analysis. Lancet Infect Dis. 2011, 11: 845-854. 10.1016/S1473-3099(11)70127-X.View ArticlePubMedGoogle Scholar
- Niël-Weise BS, Gastmeier P, Kola A, Vonberg RP, Wille JC, van den Broek PJ, Bed Head Elevation Study Group: An evidence-based recommendation on bed head elevation for mechanically ventilated patients. Crit Care. 2011, 15: R111-10.1186/cc10135.View ArticlePubMedPubMed CentralGoogle Scholar
- Petros A, Silvestri L, Booth R, Taylor N, van Saene H: Selective decontamination of the digestive tract in critically ill children: systematic review and meta-analysis. Pediatr Crit Care Med. 2012, doi:10.1097/PCC.0b013e3182417871Google Scholar
- Stonecypher K: Ventilator-associated pneumonia: the importance of oral care in intubated adults. Crit Care Nurs Q. 2010, 33: 339-347. 10.1097/CNQ.0b013e3181f649a6.View ArticlePubMedGoogle Scholar
- Rosenthal VD, Rodríguez-Calderón ME, Rodríguez-Ferrer M, Singhal T, Pawar M, Sobreyra-Oropeza M, Barkat A, Atencio-Espinoza T, Berba R, Navoa-Ng JA, Dueñas L, Ben-Jaballah N, Ozdemir D, Ersoz G, Aygun C: Findings of the International Nosocomial Infection Control Consortium (INICC), Part II: impact of a multidimensional strategy to reduce ventilator-associated pneumonia in neonatal intensive care units in 10 developing countries. Infect Control Hosp Epidemiol. 2012, 33: 704-10.1086/666342.View ArticlePubMedGoogle Scholar
- Caserta RA, Marra AR, Durão MS, Silva CV, Pavao dos Santos OF, Neves HS, Edmond MB, Timenetsky KT: A program for sustained improvement in preventing ventilator associated pneumonia in an intensive care setting. BMC Infect Dis. 2012, 12: 234-10.1186/1471-2334-12-234.View ArticlePubMedPubMed CentralGoogle Scholar
- Berenholtz SM, Pham JC, Thompson DA, Needham DM, Lubomski LH, Hyzy RC, Welsh R, Cosgrove SE, Sexton JB, Colantuoni E, Watson SR, Goeschel CA, Pronovost PJ: Collaborative cohort study of an intervention to reduce ventilator-associated pneumonia in the intensive care unit. Infect Control Hosp Epidemiol. 2011, 32: 305-314. 10.1086/658938.View ArticlePubMedGoogle Scholar
- Marwick C, Davey P: Care bundles: the holy grail of infectious risk management in hospital?. Curr Opin Infect Dis. 2009, 22: 364-369. 10.1097/QCO.0b013e32832e0736.View ArticlePubMedGoogle Scholar
- Pronovost PJ, Berenholtz SM, Ngo K, McDowell M, Holzmueller C, Haraden C, Resar R, Rainey T, Nolan T, Dorman T: Developing and pilot testing quality indicators in the intensive care unit* 1. J Crit Care. 2003, 18: 145-155. 10.1016/j.jcrc.2003.08.003.View ArticlePubMedGoogle Scholar
- Kaier K, Wilson C, Hulscher M, Wollersheim H, Huis A, Borg M, Scicluna E, Lambert ML, Palomar M, Tacconelli E, De Angelis G, Schumacher M, Wolkewitz M, Kleissle EM, Frank U: Implementing strategic bundles for infection prevention and management. Infection. 2011, 40: 225-228.View ArticlePubMedGoogle Scholar
- Bouadma L, Mourvillier B, Deiler V, Le Corre B, Lolom I, Régnier B, Wolff M, Lucet JC: A multifaceted program to prevent ventilator-associated pneumonia: impact on compliance with preventive measures. Crit Care Med. 2010, 38: 789-10.1097/CCM.0b013e3181ce21af.View ArticlePubMedGoogle Scholar
- Rello J, Afonso E, Lisboa T, Ricart M, Balsera B, Rovira A, Valles J, Diaz E, FADO Project Investigators: A care bundle approach for prevention of ventilator - associated pneumonia. Clin Microbiol Infect. 2012, 19: 363-369.View ArticlePubMedGoogle Scholar
- Moller AH, Hansen L, Jensen MS, Ehlers LH: A cost-effectiveness analysis of reducing ventilator-associated pneumonia at a Danish ICU with ventilator bundle. J Med Econ. 2011, 15: 285-292.View ArticlePubMedGoogle Scholar
- Bird D, Zambuto A, O'Donnell C, Silva J, Korn C, Burke R, Burke P, Agarwal S: Adherence to ventilator-associated pneumonia bundle and incidence of ventilator-associated pneumonia in the surgical intensive care unit. Arch Surg. 2010, 145: 465-10.1001/archsurg.2010.69.View ArticlePubMedGoogle Scholar
- Rello J, Lorente C, Bodí M, Diaz E, Ricart M, Kollef MH: Why do physicians not follow evidence-based guidelines for preventing ventilator-associated pneumonia? A survey based on the opinions of an international panel of intensivists. CHEST J. 2002, 122: 656-661. 10.1378/chest.122.2.656.View ArticleGoogle Scholar
- Lambert ML, Palomar M, Agodi A, Hiesmayr M, Lepape A, Ingenbleek A, Palencia Herrejon E, Blot S, Frank U: Prevention of ventilator-associated pneumonia in intensive care units: an international online survey. Antimicrob Resist Infect Control. 2013, 2: doi:10.1186/2047-2994-2-9Google Scholar
- Raspe HH, Hüppe A, Strech D, Taupitz J: Empfehlungen zur Begutachtung klinischer Studien durch Ethik-Kommissionen. 2012, Köln: Deutscher ÄrzteverlagGoogle Scholar
- Doppelfeld E: Aufgaben und Arbeitsweise Medizinischer Ethik-Kommissionen. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz. 2009, 52: 387-393. 10.1007/s00103-009-0824-6.View ArticlePubMedGoogle Scholar
- Lambert M, Palomar M, Agodi A, Hiesmayr M, Lepape A, Ingenbleek A, Herrejon EP, Blot S, Frank U: Data from: prevention of ventilator-associated pneumonia in intensive care units: an international online survey. Dryad Digit Repository. 2013, doi:10.5061/dryad.q1d7fGoogle Scholar
- Lambert ML, Palomar M, Agodi A, Hiesmayr M, Lepape A, Ingenbleek A, Palencia Herrejon E, Blot S, Frank U: Prevention of ventilator-associated pneumonia in intensive care units: an international online survey, additional file 1: detailed country-specific results: number responding, respondents characteristics, reported practices, attitudes. Antimicrob Resist Infect Control. 2013, 2: Doi: 10.1186/2047-2994-2-9Google Scholar
- Rello J, Lode H, Cornaglia G, Masterton R: A European care bundle for prevention of ventilator-associated pneumonia. Intensive Care Med. 2010, 36: 773-780. 10.1007/s00134-010-1841-5.View ArticlePubMedGoogle Scholar
- Zaydfudim V, Dossett LA, Starmer JM, Arbogast PG, Feurer ID, Ray WA, May AK, Pinson CW: Implementation of a real-time compliance dashboard to help reduce SICU ventilator-associated pneumonia with the ventilator bundle. Arch Surg. 2009, 144: 656-10.1001/archsurg.2009.117.View ArticlePubMedGoogle Scholar
- Bonello RS, Fletcher CE, Becker WK, Clutter KL, Arjes SL, Cook JJ, Petzel RA: An intensive care unit quality improvement collaborative in nine Department of Veterans Affairs hospitals: reducing ventilator-associated pneumonia and catheter-related bloodstream infection rates. Jt Comm J Qual Patient Saf. 2008, 34: 639-645.PubMedGoogle Scholar
- Hughes JM: Study on the efficacy of nosocomial infection control (SENIC Project): results and implications for the future. Chemotherapy. 2009, 34: 553-561.View ArticleGoogle Scholar
- Haley RW, Quade D, Freeman HE, Bennett JV: Study on the efficacy of nosocomial infection control (SENIC Project): summary of study design. Am J Epidemiol. 1980, 111: 472-485.PubMedGoogle Scholar
- Gaynes RP: Surveillance of nosocomial infections: a fundamental ingredient for quality. Infect Control Hosp Epidemiol. 1997, 18: 475-478. 10.2307/30141186.View ArticlePubMedGoogle Scholar
- Zuschneid I, Schwab F, Geffers C, Behnke M, Rüden H, Gastmeier P: Trends in ventilator - associated pneumonia rates within the German nosocomial infection surveillance system (KISS). Infect Control Hosp Epidemiol. 2007, 28: 314-318. 10.1086/507823.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2334/14/199/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.