Support Care Cancer DOI 10.1007/s00520-015-2682-0
ORIGINAL ARTICLE
Development and first data of a customized short tracheal cannula based on digital data Rainer Müller & Heike Meißner & Gunter Böttcher & Lutz Jatzwauk & Ludwig Kant & Matthias C. Schulz & Bernd Reitemeier
Received: 30 July 2014 / Accepted: 23 February 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose At the moment, there is an inadequate margin fit of commercially available stoma buttons. The aim of the present study was to develop a customized short tracheal cannula based on digital data. Furthermore, the applied material has to be evaluated considering germ colonization and appropriate cleaning procedures. Methods Computed tomographies of 53 patients who underwent laryngectomy were surveyed. Based on the digital data, a customized short tracheal cannula was created and manufactured from silicone. The new cannula was incorporated in ten patients and worn for 4 weeks. A clinical R. Müller Department of ENT, University Hospital BCarl Gustav Carus^, Technische Universität Dresden, Fetscherstr 74, 01307 Dresden, Germany
examination of an otolaryngologist and subjective assessment of the patients were carried out. Furthermore, microbiological test considering germ colonization was performed. Results The customized short tracheal cannula could be incorporated in all patients. The clinical results showed no irritation or mucosal lesions. The subjective individual evaluation by the patients was promising. The proposals for improvement could be considered. The microbiological examination revealed a higher contamination of the silicone compared to the silver cannulas. Both chemical and mechanical decontamination showed sufficient results. Conclusion A workflow for development and manufacturing of a customized short tracheal cannula from digital data could be established. The cannula is compatible to standard equipment and routine cleaning procedures. Clinical studies are required to evaluate the potential benefit for patients.
H. Meißner : B. Reitemeier (*) Department of Prosthetic Dentistry, University Hospital BCarl Gustav Carus^, Technische Universität Dresden, Fetscherstr 74, 01307 Dresden, Germany e-mail: [email protected]
Keywords Digital data . Individualization . Short tracheal cannula . Stoma button . Tracheostoma
G. Böttcher Firma KET Kunststoff-und Elasttechnik, Wachauer Str. 3, 01454 Radeberg, Germany
Introduction
L. Jatzwauk Department of Hospital Infection Control, University Hospital BCarl Gustav Carus^, Technische Universität Dresden, Fetscherstr 74, 01307 Dresden, Germany L. Kant Firma NRU Präzisionstechnik, Südstr. 3, 09221 Neukirchen, Germany M. C. Schulz Department of Oral and Maxillofacial Surgery, Medical Faculty BCarl Gustav Carus^, Technische Universität Dresden, Fetscherstr 74, 01307 Dresden, Germany
Between 1973 and 1997, a large number of head and neck cancer in northern America could be observed [1]. In patients suffering from head and neck cancer alterations of the tracheobronchial areas are found frequently [2, 3]. One major risk factor for laryngeal cancer seems to be smoking [4]. In patients suffering from an extended laryngeal carcinoma, a laryngectomy is indicated [5]. Generally, the oncologic therapy is stressful and limiting the patients’ daily life activities [6]. In particular, patients who underwent laryngectomy might suffer from local complications like abrasive endotracheal mucosa lesion and tracheal stenosis cause by inadequate margin fit of the tracheal cannula. For those patients, tracheal cannulae
Support Care Cancer
shaped like a quarter arc of circle as described by Luer and Trosseau seem not to be the appropriate way of treatment. Frequently, these cannulae cause alterations of the tracheal mucosa and the tracheal cartilage (Fig. 1). Proliferation of the endotracheal mucosa and thus, blood sputum were reported [7, 8]. These tracheal stenoses were observed in about 10 % of the patients who underwent laryngectomy [7]. All patients examined in the mentioned study were supplied with tracheal cannulae shaped like quarter of circle. However, only 30 % of the patients accepted the complete abandonment as a potential long-term solution [8]. Hence, a customized short tracheal cannula made of poly-methyl-methacrylate was developed and clinically applied by Böhme [7]. Those customized cannulae had an improved margin fit and thus, the endotracheal proliferations and consecutively, the risk of bleeding could be reduced. However, the air leakage and the risk of ejection during a fit of coughing were not entirely avoided. The application of customized titanium cannulae could not eliminate these drawbacks, likewise [9]. Frequently, industrially fabricated stoma buttons do not correlate with the individual anatomical situation of the tracheostoma and the adjacent tissue. Air leakage causing ambient noise and thus, problems to speak when using shunt valves might occur [10, 11]. For these patients, talking might be arduous and exhausting. Furthermore, there is the risk to eject the button during a fit of coughing. Industrial fabricated short tracheal cannulae made of plastic are lacking a perfect margin fit, likewise. Thus, there is currently no satisfying solution.
Fig. 1 Proliferation of the endotracheal mucosa (ventral wall) caused by tracheal cannula
The aim of the present study was to develop a customized tracheal cannula for patients needing a stoma button or a short tracheal cannula after laryngectomy. The individualization of the tracheal region located between tracheostoma and the transitional part to the natural course of the trachea using anatomical and morphological data was intended. In particular, the angle of the short tracheal cannula was adapted according to the individual situation. To approach this individualization, digital data was used. Additionally, the colonization of the applied materials with germs and cleaning procedures was valuated. Furthermore, ten patients supplied with preproduction models were examined by an experienced otolaryngologist and completed a questionnaire.
Materials and methods The study protocol followed the ethical standards of the Declaration of Helsinki and was approved by the ethical review committee of the University Hospital BCarl Gustav Carus^, Technische Universität Dresden, Dresden (file number EK 55022009). For the study, computed tomography scans of 53 patients who underwent laryngectomy were evaluated using a digital planning software (coDiagnostixx 5.6, IVS Solutions AG, Chemnitz, Germany). The distance of the caudal and cranial wall of the artificial trachea directly at the tracheostoma (A1), at the transition to the trachea (A2), and the distance between the ventral and dorsal wall of the trachea (A3) were quantified (Fig. 2 left). Additionally, the angles between the skin level and tracheostoma (w1) as well as between the tracheostoma and the trachea (w2) were measured (Fig. 2 right). Of the 53 computed tomography scans, 41 patients (30 male, 11 female) with an average age of 56.2±12.3 years were included in the study. Twelve computed tomography scans were excluded because the evaluation of the tracheostomal area was not possible. Medians, means, and standard deviations of these 41 patients were calculated. Based on these data, the customized short tracheal cannula was created according
Fig. 2 Schematic drawing of the distances and angles measured in the computed tomography scans. Left – Distances of the ventral and caudal wall of the tracheostoma and the trachea. Right – Angles meausured between the tracheostoma and the trachea
Support Care Cancer
to the postoperative anatomical situation of the patient. The fixation of the tracheal cannula was realized by using commercially available adherent patches (e.g., Laryvox® Tape Comfort; Fa. Fahl, Köln, Germany, Fig. 3). Thus, leakage tightness could be achieved. Then, based on the achieved data, the short cannula was digitally fixed air-tight to the patches. Following, the newly developed tracheal cannula was manufactured using an injection die casting procedure by KET Kunststoff und Elasttechnik (Radeberg, Germany) from biocompatible silicone Elastosil® P7687 (Wacker Chemie, München, Germany). In a second step, ten randomly selected patients were supplied with the new developed tracheal cannula. The patients were instructed to wear the customized tracheal cannula for 4 weeks. Directly after incorporation and after 4 weeks, the patients were clinically examined by an experienced otolaryngologist regarding accuracy of fit, bleeding, proliferation of tracheal mucosa, and air leakage. Furthermore, transoral/ transnasal endoscopic findings were recorded. Subsequently, an individual evaluation was performed using partly standardized questionnaires. Those questionnaires included individual information regarding the recently used tracheal devices, the length of wearing time as well as subjective evaluation of the wearing comfort, leak tightness, influence on speech, fixation on the circular patches, production of mucus, used devices, and frequency of cleaning. To examine the colonization with germs of the applied biocompatible silicone, the following microbiological tests were carried out in a standardized manner. Material obtained from silver tracheal cannulae (Servona, Troisdorf, Germany) served as control. Each ten sample devices of a diameter of 8 and a height of 1 mm were sterilized using formaldehyde gas sterilization (Formaldehyd-GasSterilisator A90, WEBECO, Bad Schwartau, Germany) and used for every testing. First, the samples were inoculated with suspensions of the following representative germs: Staphylococcus epidermidis Pseudomonas aeruginosa Candida albicans
Fig. 3 Circular self-adhering patch Laryvox® - Tape Comfort
After inoculation, the samples were incubated at 37 °C for 24 h. Subsequently, the quantity of germs was measured following the instructions BQuantification of germs in liquids using direct transfer^ (BBestimmung der Keimzahl in Flüssigkeiten mittels Direkttransfer^ and BQuantification of germs using membrane filtration^ Keimzahlbestimmung mittels Membranfiltration) following Ph.Eur.5 (2.6.12) [12]. Following, the reduction of the germ quantity was evaluated. Therefore, each ten sterilized sample devices were used, likewise. In the previous contamination tests, the applied silicone showed a pronounced quantity of germs. Thus, the medical approved silicone SILPURAN 6600 (Wacker Chemie, Munich, Germany) was used for the following test and will be used exclusively. To evaluate the effectiveness of different decontamination procedures, Pseudomonas aeruginosa (27857) which is characteristic for biofilms was applied. Identity and purity of the bacteria were checked. For contamination, the samples were stored in culture medium and incubated at 37 °C for 48 h followed by air-drying at 36 °C for 8 h. Each ten samples were treated using different decontamination procedures: – – –
Brushing for 1 min and 30 s under running tap water (Optibrush® plus Kanülenreinigungsbürste; Fahl, Cologne, Germany) Dip disinfection for 5 min in dental disinfection solution (WL clean 4 %; Alpro, St. Georgen, Germany) Disinfection for 30 min using Sekusept plus 4 % (Ecolab, Monheim am Rhein, Germany)
To interrupt the disinfection process, the samples were stored in a sterile neutralizing solution (0.9 % saline solution; 0.3 % saponine; 0.1 % histidine; 0.1 % cystein; 0.1 % tween). Subsequently, the samples were plated on Columbia blood agar and incubated at 37 °C for 24 h. The colony-forming units were quantified.
Results The data for the creation of the customized short tracheal cannula are shown in Table 1. Based on the measurements of the computed tomographies, an angle of 60° was calculated as the preferred angle between tracheal cannula and trachea. Regarding the diameter, three different diameters were obtained to create the conical part of the cannula. The resulting short tracheal cannula is shown in Fig. 4. The marginal fit of the cannula fixed with a circular patch is demonstrated in Fig. 5. Commercial available equipment like the HME cassette (Provox HME–Kassetten (ATOS, Hörby, Sweden) is simply attachable to the cannula (Fig. 5).
Support Care Cancer Table 1 Distribution of the distances and angles measured in the computed tomography scans by sex Sex
Distance (mm)
Length (mm)
Angle (°)
A1
A2
A3
L
W1
W2
14 13 3
10 9 2
18 17 3
29 30 5
64 62 10
127 128 10
15 15 3
10 11 4
14 13 2
20 22 11
60 61 14
130 131 6
Male Median Mean Standard deviation Female Median Mean Standard deviation
The clinical evaluation of the otolaryngologist was promising. The endoscopical findings showed no irritation of the tracheal mucosa after incorporation. An adjustment in length was not necessary. After 4 weeks, eight out of the ten patients were available for re-evaluation. The fixation of the cannula using the circula patch enabled a tight fit of the device. Air leakage could not be detected, and when speech was examined, no ambient noise was found. Using the short cannula in combination with the circular patch, no ejection of the cannula could be observed during a provoked fit of coughing. The questionnaires were returned by eight patients. Five patients reported complete satisfaction with the new tracheal cannula. The three other patients complained about minor issues regarding difficulties to clean the angled parts of the cannula or the position of the handle. No irritation of the adjacent mucosal tissues, e.g., bleeding, increased mucosal production, or obstruction, was reported by the patients. The tight fit of the circular patch and the cannula were evaluated positively, in particular while speaking. None of the patients experienced an ejection of the cannula during a fit of cough. The handling and the connection of commercially available equipment, e.g., Provox HME–cassettes (ATOS, Hörby, Sweden), were easily possible.
Fig. 4 The customized short tracheal cannula (view on the endotracheal part)
Fig. 5 Fixation of the cannula using the Laryvox® - Tape Comfort. A HME cassette on the customized short tracheal cannula is in situ
The microbiological examination showed differences in the quantity of contamination. A mean of
ORIGINAL ARTICLE
Development and first data of a customized short tracheal cannula based on digital data Rainer Müller & Heike Meißner & Gunter Böttcher & Lutz Jatzwauk & Ludwig Kant & Matthias C. Schulz & Bernd Reitemeier
Received: 30 July 2014 / Accepted: 23 February 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose At the moment, there is an inadequate margin fit of commercially available stoma buttons. The aim of the present study was to develop a customized short tracheal cannula based on digital data. Furthermore, the applied material has to be evaluated considering germ colonization and appropriate cleaning procedures. Methods Computed tomographies of 53 patients who underwent laryngectomy were surveyed. Based on the digital data, a customized short tracheal cannula was created and manufactured from silicone. The new cannula was incorporated in ten patients and worn for 4 weeks. A clinical R. Müller Department of ENT, University Hospital BCarl Gustav Carus^, Technische Universität Dresden, Fetscherstr 74, 01307 Dresden, Germany
examination of an otolaryngologist and subjective assessment of the patients were carried out. Furthermore, microbiological test considering germ colonization was performed. Results The customized short tracheal cannula could be incorporated in all patients. The clinical results showed no irritation or mucosal lesions. The subjective individual evaluation by the patients was promising. The proposals for improvement could be considered. The microbiological examination revealed a higher contamination of the silicone compared to the silver cannulas. Both chemical and mechanical decontamination showed sufficient results. Conclusion A workflow for development and manufacturing of a customized short tracheal cannula from digital data could be established. The cannula is compatible to standard equipment and routine cleaning procedures. Clinical studies are required to evaluate the potential benefit for patients.
H. Meißner : B. Reitemeier (*) Department of Prosthetic Dentistry, University Hospital BCarl Gustav Carus^, Technische Universität Dresden, Fetscherstr 74, 01307 Dresden, Germany e-mail: [email protected]
Keywords Digital data . Individualization . Short tracheal cannula . Stoma button . Tracheostoma
G. Böttcher Firma KET Kunststoff-und Elasttechnik, Wachauer Str. 3, 01454 Radeberg, Germany
Introduction
L. Jatzwauk Department of Hospital Infection Control, University Hospital BCarl Gustav Carus^, Technische Universität Dresden, Fetscherstr 74, 01307 Dresden, Germany L. Kant Firma NRU Präzisionstechnik, Südstr. 3, 09221 Neukirchen, Germany M. C. Schulz Department of Oral and Maxillofacial Surgery, Medical Faculty BCarl Gustav Carus^, Technische Universität Dresden, Fetscherstr 74, 01307 Dresden, Germany
Between 1973 and 1997, a large number of head and neck cancer in northern America could be observed [1]. In patients suffering from head and neck cancer alterations of the tracheobronchial areas are found frequently [2, 3]. One major risk factor for laryngeal cancer seems to be smoking [4]. In patients suffering from an extended laryngeal carcinoma, a laryngectomy is indicated [5]. Generally, the oncologic therapy is stressful and limiting the patients’ daily life activities [6]. In particular, patients who underwent laryngectomy might suffer from local complications like abrasive endotracheal mucosa lesion and tracheal stenosis cause by inadequate margin fit of the tracheal cannula. For those patients, tracheal cannulae
Support Care Cancer
shaped like a quarter arc of circle as described by Luer and Trosseau seem not to be the appropriate way of treatment. Frequently, these cannulae cause alterations of the tracheal mucosa and the tracheal cartilage (Fig. 1). Proliferation of the endotracheal mucosa and thus, blood sputum were reported [7, 8]. These tracheal stenoses were observed in about 10 % of the patients who underwent laryngectomy [7]. All patients examined in the mentioned study were supplied with tracheal cannulae shaped like quarter of circle. However, only 30 % of the patients accepted the complete abandonment as a potential long-term solution [8]. Hence, a customized short tracheal cannula made of poly-methyl-methacrylate was developed and clinically applied by Böhme [7]. Those customized cannulae had an improved margin fit and thus, the endotracheal proliferations and consecutively, the risk of bleeding could be reduced. However, the air leakage and the risk of ejection during a fit of coughing were not entirely avoided. The application of customized titanium cannulae could not eliminate these drawbacks, likewise [9]. Frequently, industrially fabricated stoma buttons do not correlate with the individual anatomical situation of the tracheostoma and the adjacent tissue. Air leakage causing ambient noise and thus, problems to speak when using shunt valves might occur [10, 11]. For these patients, talking might be arduous and exhausting. Furthermore, there is the risk to eject the button during a fit of coughing. Industrial fabricated short tracheal cannulae made of plastic are lacking a perfect margin fit, likewise. Thus, there is currently no satisfying solution.
Fig. 1 Proliferation of the endotracheal mucosa (ventral wall) caused by tracheal cannula
The aim of the present study was to develop a customized tracheal cannula for patients needing a stoma button or a short tracheal cannula after laryngectomy. The individualization of the tracheal region located between tracheostoma and the transitional part to the natural course of the trachea using anatomical and morphological data was intended. In particular, the angle of the short tracheal cannula was adapted according to the individual situation. To approach this individualization, digital data was used. Additionally, the colonization of the applied materials with germs and cleaning procedures was valuated. Furthermore, ten patients supplied with preproduction models were examined by an experienced otolaryngologist and completed a questionnaire.
Materials and methods The study protocol followed the ethical standards of the Declaration of Helsinki and was approved by the ethical review committee of the University Hospital BCarl Gustav Carus^, Technische Universität Dresden, Dresden (file number EK 55022009). For the study, computed tomography scans of 53 patients who underwent laryngectomy were evaluated using a digital planning software (coDiagnostixx 5.6, IVS Solutions AG, Chemnitz, Germany). The distance of the caudal and cranial wall of the artificial trachea directly at the tracheostoma (A1), at the transition to the trachea (A2), and the distance between the ventral and dorsal wall of the trachea (A3) were quantified (Fig. 2 left). Additionally, the angles between the skin level and tracheostoma (w1) as well as between the tracheostoma and the trachea (w2) were measured (Fig. 2 right). Of the 53 computed tomography scans, 41 patients (30 male, 11 female) with an average age of 56.2±12.3 years were included in the study. Twelve computed tomography scans were excluded because the evaluation of the tracheostomal area was not possible. Medians, means, and standard deviations of these 41 patients were calculated. Based on these data, the customized short tracheal cannula was created according
Fig. 2 Schematic drawing of the distances and angles measured in the computed tomography scans. Left – Distances of the ventral and caudal wall of the tracheostoma and the trachea. Right – Angles meausured between the tracheostoma and the trachea
Support Care Cancer
to the postoperative anatomical situation of the patient. The fixation of the tracheal cannula was realized by using commercially available adherent patches (e.g., Laryvox® Tape Comfort; Fa. Fahl, Köln, Germany, Fig. 3). Thus, leakage tightness could be achieved. Then, based on the achieved data, the short cannula was digitally fixed air-tight to the patches. Following, the newly developed tracheal cannula was manufactured using an injection die casting procedure by KET Kunststoff und Elasttechnik (Radeberg, Germany) from biocompatible silicone Elastosil® P7687 (Wacker Chemie, München, Germany). In a second step, ten randomly selected patients were supplied with the new developed tracheal cannula. The patients were instructed to wear the customized tracheal cannula for 4 weeks. Directly after incorporation and after 4 weeks, the patients were clinically examined by an experienced otolaryngologist regarding accuracy of fit, bleeding, proliferation of tracheal mucosa, and air leakage. Furthermore, transoral/ transnasal endoscopic findings were recorded. Subsequently, an individual evaluation was performed using partly standardized questionnaires. Those questionnaires included individual information regarding the recently used tracheal devices, the length of wearing time as well as subjective evaluation of the wearing comfort, leak tightness, influence on speech, fixation on the circular patches, production of mucus, used devices, and frequency of cleaning. To examine the colonization with germs of the applied biocompatible silicone, the following microbiological tests were carried out in a standardized manner. Material obtained from silver tracheal cannulae (Servona, Troisdorf, Germany) served as control. Each ten sample devices of a diameter of 8 and a height of 1 mm were sterilized using formaldehyde gas sterilization (Formaldehyd-GasSterilisator A90, WEBECO, Bad Schwartau, Germany) and used for every testing. First, the samples were inoculated with suspensions of the following representative germs: Staphylococcus epidermidis Pseudomonas aeruginosa Candida albicans
Fig. 3 Circular self-adhering patch Laryvox® - Tape Comfort
After inoculation, the samples were incubated at 37 °C for 24 h. Subsequently, the quantity of germs was measured following the instructions BQuantification of germs in liquids using direct transfer^ (BBestimmung der Keimzahl in Flüssigkeiten mittels Direkttransfer^ and BQuantification of germs using membrane filtration^ Keimzahlbestimmung mittels Membranfiltration) following Ph.Eur.5 (2.6.12) [12]. Following, the reduction of the germ quantity was evaluated. Therefore, each ten sterilized sample devices were used, likewise. In the previous contamination tests, the applied silicone showed a pronounced quantity of germs. Thus, the medical approved silicone SILPURAN 6600 (Wacker Chemie, Munich, Germany) was used for the following test and will be used exclusively. To evaluate the effectiveness of different decontamination procedures, Pseudomonas aeruginosa (27857) which is characteristic for biofilms was applied. Identity and purity of the bacteria were checked. For contamination, the samples were stored in culture medium and incubated at 37 °C for 48 h followed by air-drying at 36 °C for 8 h. Each ten samples were treated using different decontamination procedures: – – –
Brushing for 1 min and 30 s under running tap water (Optibrush® plus Kanülenreinigungsbürste; Fahl, Cologne, Germany) Dip disinfection for 5 min in dental disinfection solution (WL clean 4 %; Alpro, St. Georgen, Germany) Disinfection for 30 min using Sekusept plus 4 % (Ecolab, Monheim am Rhein, Germany)
To interrupt the disinfection process, the samples were stored in a sterile neutralizing solution (0.9 % saline solution; 0.3 % saponine; 0.1 % histidine; 0.1 % cystein; 0.1 % tween). Subsequently, the samples were plated on Columbia blood agar and incubated at 37 °C for 24 h. The colony-forming units were quantified.
Results The data for the creation of the customized short tracheal cannula are shown in Table 1. Based on the measurements of the computed tomographies, an angle of 60° was calculated as the preferred angle between tracheal cannula and trachea. Regarding the diameter, three different diameters were obtained to create the conical part of the cannula. The resulting short tracheal cannula is shown in Fig. 4. The marginal fit of the cannula fixed with a circular patch is demonstrated in Fig. 5. Commercial available equipment like the HME cassette (Provox HME–Kassetten (ATOS, Hörby, Sweden) is simply attachable to the cannula (Fig. 5).
Support Care Cancer Table 1 Distribution of the distances and angles measured in the computed tomography scans by sex Sex
Distance (mm)
Length (mm)
Angle (°)
A1
A2
A3
L
W1
W2
14 13 3
10 9 2
18 17 3
29 30 5
64 62 10
127 128 10
15 15 3
10 11 4
14 13 2
20 22 11
60 61 14
130 131 6
Male Median Mean Standard deviation Female Median Mean Standard deviation
The clinical evaluation of the otolaryngologist was promising. The endoscopical findings showed no irritation of the tracheal mucosa after incorporation. An adjustment in length was not necessary. After 4 weeks, eight out of the ten patients were available for re-evaluation. The fixation of the cannula using the circula patch enabled a tight fit of the device. Air leakage could not be detected, and when speech was examined, no ambient noise was found. Using the short cannula in combination with the circular patch, no ejection of the cannula could be observed during a provoked fit of coughing. The questionnaires were returned by eight patients. Five patients reported complete satisfaction with the new tracheal cannula. The three other patients complained about minor issues regarding difficulties to clean the angled parts of the cannula or the position of the handle. No irritation of the adjacent mucosal tissues, e.g., bleeding, increased mucosal production, or obstruction, was reported by the patients. The tight fit of the circular patch and the cannula were evaluated positively, in particular while speaking. None of the patients experienced an ejection of the cannula during a fit of cough. The handling and the connection of commercially available equipment, e.g., Provox HME–cassettes (ATOS, Hörby, Sweden), were easily possible.
Fig. 4 The customized short tracheal cannula (view on the endotracheal part)
Fig. 5 Fixation of the cannula using the Laryvox® - Tape Comfort. A HME cassette on the customized short tracheal cannula is in situ
The microbiological examination showed differences in the quantity of contamination. A mean of
