Partial oral treatment of endocarditis
Background Guidelines for the treatment of left-sided infective endocarditis (IE) recommend 4 to 6 weeks of intravenous antibiotics. Conversion from intravenous to oral antibiotics in clinically stabilized patients could reduce the side effects associated with intravenous treatment and shorten the l...
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| Veröffentlicht in: | The American heart journal 2013-02, Vol.165 (2), p.116-122 |
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| creator | Iversen, Kasper, MD, DMSc Høst, Nis, MD, PhD Bruun, Niels Eske, MD, DMSc Elming, Hanne, MD, PhD Pump, Bettina, MD, DMSc Christensen, Jens Jørgen, MD, DMSc Gill, Sabine, PhD Rosenvinge, Flemming, MD Wiggers, Henrik, MD, DMSc Fuursted, Kurt, MD, DMSc Holst-Hansen, Claus, MD, PhD Korup, Eva, MD, PhD Schønheyder, Henrik Carl, MD, DMSc Hassager, Christian, MD, DMSc Høfsten, Dan, MD, PhD Larsen, Jannik Helweg, MD, DMSc Moser, Claus, MD, PhD Ihlemann, Nikolaj, MD, PhD Bundgaard, Henning, MD, DMSc |
| description | Background Guidelines for the treatment of left-sided infective endocarditis (IE) recommend 4 to 6 weeks of intravenous antibiotics. Conversion from intravenous to oral antibiotics in clinically stabilized patients could reduce the side effects associated with intravenous treatment and shorten the length of hospital stay. Evidence supporting partial oral therapy as an alternative to the routinely recommended continued parenteral therapy is scarce, although observational data suggest that this strategy may be safe and effective. Study Design This is a noninferiority, multicenter, prospective, randomized, open-label study of partial oral treatment with antibiotics compared with full parenteral treatment in left-sided IE. Stable patients (n = 400) with streptococci, staphylococci, or enterococci infecting the mitral valve or the aortic valve will be included. After a minimum of 10 days of parenteral treatment, stable patients are randomized to oral therapy or unchanged parenteral therapy. Recommendations for oral treatment have been developed based on minimum inhibitory concentrations and pharmacokinetic calculations. Patients will be followed up for 6 months after completion of antibiotic therapy. The primary end point is a composition of all-cause mortality, unplanned cardiac surgery, embolic events, and relapse of positive blood cultures with the primary pathogen. Conclusion The Partial Oral Treatment of Endocarditis study tests the hypothesis that partial oral antibiotic treatment is as efficient and safe as parenteral therapy in left-sided IE. The trial is justified by a review of the literature, by pharmacokinetic calculations, and by our own experience. |
| doi_str_mv | 10.1016/j.ahj.2012.11.006 |
| format | Article |
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Conversion from intravenous to oral antibiotics in clinically stabilized patients could reduce the side effects associated with intravenous treatment and shorten the length of hospital stay. Evidence supporting partial oral therapy as an alternative to the routinely recommended continued parenteral therapy is scarce, although observational data suggest that this strategy may be safe and effective. Study Design This is a noninferiority, multicenter, prospective, randomized, open-label study of partial oral treatment with antibiotics compared with full parenteral treatment in left-sided IE. Stable patients (n = 400) with streptococci, staphylococci, or enterococci infecting the mitral valve or the aortic valve will be included. After a minimum of 10 days of parenteral treatment, stable patients are randomized to oral therapy or unchanged parenteral therapy. Recommendations for oral treatment have been developed based on minimum inhibitory concentrations and pharmacokinetic calculations. Patients will be followed up for 6 months after completion of antibiotic therapy. The primary end point is a composition of all-cause mortality, unplanned cardiac surgery, embolic events, and relapse of positive blood cultures with the primary pathogen. Conclusion The Partial Oral Treatment of Endocarditis study tests the hypothesis that partial oral antibiotic treatment is as efficient and safe as parenteral therapy in left-sided IE. The trial is justified by a review of the literature, by pharmacokinetic calculations, and by our own experience.</description><identifier>ISSN: 0002-8703</identifier><identifier>EISSN: 1097-6744</identifier><identifier>DOI: 10.1016/j.ahj.2012.11.006</identifier><identifier>PMID: 23351813</identifier><identifier>CODEN: AHJOA2</identifier><language>eng</language><publisher>United States: Mosby, Inc</publisher><subject>Administration, Oral ; Adult ; Aged ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - pharmacokinetics ; Antibiotics ; Blood ; Cardiovascular ; Dose-Response Relationship, Drug ; Drug therapy ; Electrodes ; Endocarditis, Bacterial - blood ; Endocarditis, Bacterial - drug therapy ; Female ; Follow-Up Studies ; Heart ; Heart surgery ; Hospitalization ; Humans ; Injections, Intravenous ; Male ; Middle Aged ; Mortality ; Prospective Studies ; Prostheses ; Quality of life ; Studies ; Success ; Treatment Outcome</subject><ispartof>The American heart journal, 2013-02, Vol.165 (2), p.116-122</ispartof><rights>Mosby, Inc.</rights><rights>2013 Mosby, Inc.</rights><rights>Copyright © 2013 Mosby, Inc. All rights reserved.</rights><rights>Copyright Elsevier Limited Feb 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c436t-649ef9e9cbfcc5bce9edca064c0e6d8c98d4788330e28746e95073bdd2825b7e3</citedby><cites>FETCH-LOGICAL-c436t-649ef9e9cbfcc5bce9edca064c0e6d8c98d4788330e28746e95073bdd2825b7e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1644836469?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,778,782,3539,27907,27908,45978,64366,64368,64370,72220</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23351813$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iversen, Kasper, MD, DMSc</creatorcontrib><creatorcontrib>Høst, Nis, MD, PhD</creatorcontrib><creatorcontrib>Bruun, Niels Eske, MD, DMSc</creatorcontrib><creatorcontrib>Elming, Hanne, MD, PhD</creatorcontrib><creatorcontrib>Pump, Bettina, MD, DMSc</creatorcontrib><creatorcontrib>Christensen, Jens Jørgen, MD, DMSc</creatorcontrib><creatorcontrib>Gill, Sabine, PhD</creatorcontrib><creatorcontrib>Rosenvinge, Flemming, MD</creatorcontrib><creatorcontrib>Wiggers, Henrik, MD, DMSc</creatorcontrib><creatorcontrib>Fuursted, Kurt, MD, DMSc</creatorcontrib><creatorcontrib>Holst-Hansen, Claus, MD, PhD</creatorcontrib><creatorcontrib>Korup, Eva, MD, PhD</creatorcontrib><creatorcontrib>Schønheyder, Henrik Carl, MD, DMSc</creatorcontrib><creatorcontrib>Hassager, Christian, MD, DMSc</creatorcontrib><creatorcontrib>Høfsten, Dan, MD, PhD</creatorcontrib><creatorcontrib>Larsen, Jannik Helweg, MD, DMSc</creatorcontrib><creatorcontrib>Moser, Claus, MD, PhD</creatorcontrib><creatorcontrib>Ihlemann, Nikolaj, MD, PhD</creatorcontrib><creatorcontrib>Bundgaard, Henning, MD, DMSc</creatorcontrib><title>Partial oral treatment of endocarditis</title><title>The American heart journal</title><addtitle>Am Heart J</addtitle><description>Background Guidelines for the treatment of left-sided infective endocarditis (IE) recommend 4 to 6 weeks of intravenous antibiotics. Conversion from intravenous to oral antibiotics in clinically stabilized patients could reduce the side effects associated with intravenous treatment and shorten the length of hospital stay. Evidence supporting partial oral therapy as an alternative to the routinely recommended continued parenteral therapy is scarce, although observational data suggest that this strategy may be safe and effective. Study Design This is a noninferiority, multicenter, prospective, randomized, open-label study of partial oral treatment with antibiotics compared with full parenteral treatment in left-sided IE. Stable patients (n = 400) with streptococci, staphylococci, or enterococci infecting the mitral valve or the aortic valve will be included. After a minimum of 10 days of parenteral treatment, stable patients are randomized to oral therapy or unchanged parenteral therapy. Recommendations for oral treatment have been developed based on minimum inhibitory concentrations and pharmacokinetic calculations. Patients will be followed up for 6 months after completion of antibiotic therapy. The primary end point is a composition of all-cause mortality, unplanned cardiac surgery, embolic events, and relapse of positive blood cultures with the primary pathogen. Conclusion The Partial Oral Treatment of Endocarditis study tests the hypothesis that partial oral antibiotic treatment is as efficient and safe as parenteral therapy in left-sided IE. The trial is justified by a review of the literature, by pharmacokinetic calculations, and by our own experience.</description><subject>Administration, Oral</subject><subject>Adult</subject><subject>Aged</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - pharmacokinetics</subject><subject>Antibiotics</subject><subject>Blood</subject><subject>Cardiovascular</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug therapy</subject><subject>Electrodes</subject><subject>Endocarditis, Bacterial - blood</subject><subject>Endocarditis, Bacterial - drug therapy</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Heart</subject><subject>Heart surgery</subject><subject>Hospitalization</subject><subject>Humans</subject><subject>Injections, Intravenous</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Prospective Studies</subject><subject>Prostheses</subject><subject>Quality of life</subject><subject>Studies</subject><subject>Success</subject><subject>Treatment Outcome</subject><issn>0002-8703</issn><issn>1097-6744</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kcFq3DAQhkVpaDZJH6CXslAoudiZkWRZphAooU0CCyk0PQtZGlO5XjuVvIG8fWV220IOuUgIvv9H8w1j7xBKBFQXfWl_9iUH5CViCaBesRVCUxeqlvI1WwEAL3QN4pidpNTnp-JavWHHXIgKNYoV-_jNxjnYYT3FfMyR7LylcV5P3ZpGPzkbfZhDOmNHnR0SvT3cp-zH1y_3VzfF5u769urzpnBSqLlQsqGuoca1nXNV66gh7ywo6YCU167RXtZaCwHEdS0VNRXUovWea161NYlTdr7vfYjT7x2l2WxDcjQMdqRplwwuIFZaVRn98Aztp10c8-8MKim1UFI1mcI95eKUUqTOPMSwtfHJIJhFoulNlmgWiQbRZEU58_7QvGu35P8l_lrLwKc9QFnFY6Bokgs0OvIhkpuNn8KL9ZfP0m4IY3B2-EVPlP5PYRI3YL4vW1yWiBxACynFH-HZlKw</recordid><startdate>20130201</startdate><enddate>20130201</enddate><creator>Iversen, Kasper, MD, DMSc</creator><creator>Høst, Nis, MD, PhD</creator><creator>Bruun, Niels Eske, MD, DMSc</creator><creator>Elming, Hanne, MD, PhD</creator><creator>Pump, Bettina, MD, DMSc</creator><creator>Christensen, Jens Jørgen, MD, DMSc</creator><creator>Gill, Sabine, PhD</creator><creator>Rosenvinge, Flemming, MD</creator><creator>Wiggers, Henrik, MD, DMSc</creator><creator>Fuursted, Kurt, MD, DMSc</creator><creator>Holst-Hansen, Claus, MD, PhD</creator><creator>Korup, Eva, MD, PhD</creator><creator>Schønheyder, Henrik Carl, MD, DMSc</creator><creator>Hassager, Christian, MD, DMSc</creator><creator>Høfsten, Dan, MD, PhD</creator><creator>Larsen, Jannik Helweg, MD, DMSc</creator><creator>Moser, Claus, MD, PhD</creator><creator>Ihlemann, Nikolaj, MD, PhD</creator><creator>Bundgaard, Henning, MD, DMSc</creator><general>Mosby, Inc</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QO</scope><scope>7RV</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20130201</creationdate><title>Partial oral treatment of endocarditis</title><author>Iversen, Kasper, MD, DMSc ; Høst, Nis, MD, PhD ; Bruun, Niels Eske, MD, DMSc ; Elming, Hanne, MD, PhD ; Pump, Bettina, MD, DMSc ; Christensen, Jens Jørgen, MD, DMSc ; Gill, Sabine, PhD ; Rosenvinge, Flemming, MD ; Wiggers, Henrik, MD, DMSc ; Fuursted, Kurt, MD, DMSc ; Holst-Hansen, Claus, MD, PhD ; Korup, Eva, MD, PhD ; Schønheyder, Henrik Carl, MD, DMSc ; Hassager, Christian, MD, DMSc ; Høfsten, Dan, MD, PhD ; Larsen, Jannik Helweg, MD, DMSc ; Moser, Claus, MD, PhD ; Ihlemann, Nikolaj, MD, PhD ; Bundgaard, Henning, MD, DMSc</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c436t-649ef9e9cbfcc5bce9edca064c0e6d8c98d4788330e28746e95073bdd2825b7e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Administration, Oral</topic><topic>Adult</topic><topic>Aged</topic><topic>Anti-Bacterial Agents - administration & dosage</topic><topic>Anti-Bacterial Agents - pharmacokinetics</topic><topic>Antibiotics</topic><topic>Blood</topic><topic>Cardiovascular</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug therapy</topic><topic>Electrodes</topic><topic>Endocarditis, Bacterial - blood</topic><topic>Endocarditis, Bacterial - drug therapy</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Heart</topic><topic>Heart surgery</topic><topic>Hospitalization</topic><topic>Humans</topic><topic>Injections, Intravenous</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Prospective Studies</topic><topic>Prostheses</topic><topic>Quality of life</topic><topic>Studies</topic><topic>Success</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iversen, Kasper, MD, DMSc</creatorcontrib><creatorcontrib>Høst, Nis, MD, PhD</creatorcontrib><creatorcontrib>Bruun, Niels Eske, MD, DMSc</creatorcontrib><creatorcontrib>Elming, Hanne, MD, PhD</creatorcontrib><creatorcontrib>Pump, Bettina, MD, DMSc</creatorcontrib><creatorcontrib>Christensen, Jens Jørgen, MD, DMSc</creatorcontrib><creatorcontrib>Gill, Sabine, PhD</creatorcontrib><creatorcontrib>Rosenvinge, Flemming, MD</creatorcontrib><creatorcontrib>Wiggers, Henrik, MD, DMSc</creatorcontrib><creatorcontrib>Fuursted, Kurt, MD, DMSc</creatorcontrib><creatorcontrib>Holst-Hansen, Claus, MD, PhD</creatorcontrib><creatorcontrib>Korup, Eva, MD, PhD</creatorcontrib><creatorcontrib>Schønheyder, Henrik Carl, MD, DMSc</creatorcontrib><creatorcontrib>Hassager, Christian, MD, DMSc</creatorcontrib><creatorcontrib>Høfsten, Dan, MD, PhD</creatorcontrib><creatorcontrib>Larsen, Jannik Helweg, MD, DMSc</creatorcontrib><creatorcontrib>Moser, Claus, MD, PhD</creatorcontrib><creatorcontrib>Ihlemann, Nikolaj, MD, PhD</creatorcontrib><creatorcontrib>Bundgaard, Henning, MD, DMSc</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Physical Education Index</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>The American heart journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iversen, Kasper, MD, DMSc</au><au>Høst, Nis, MD, PhD</au><au>Bruun, Niels Eske, MD, DMSc</au><au>Elming, Hanne, MD, PhD</au><au>Pump, Bettina, MD, DMSc</au><au>Christensen, Jens Jørgen, MD, DMSc</au><au>Gill, Sabine, PhD</au><au>Rosenvinge, Flemming, MD</au><au>Wiggers, Henrik, MD, DMSc</au><au>Fuursted, Kurt, MD, DMSc</au><au>Holst-Hansen, Claus, MD, PhD</au><au>Korup, Eva, MD, PhD</au><au>Schønheyder, Henrik Carl, MD, DMSc</au><au>Hassager, Christian, MD, DMSc</au><au>Høfsten, Dan, MD, PhD</au><au>Larsen, Jannik Helweg, MD, DMSc</au><au>Moser, Claus, MD, PhD</au><au>Ihlemann, Nikolaj, MD, PhD</au><au>Bundgaard, Henning, MD, DMSc</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Partial oral treatment of endocarditis</atitle><jtitle>The American heart journal</jtitle><addtitle>Am Heart J</addtitle><date>2013-02-01</date><risdate>2013</risdate><volume>165</volume><issue>2</issue><spage>116</spage><epage>122</epage><pages>116-122</pages><issn>0002-8703</issn><eissn>1097-6744</eissn><coden>AHJOA2</coden><abstract>Background Guidelines for the treatment of left-sided infective endocarditis (IE) recommend 4 to 6 weeks of intravenous antibiotics. Conversion from intravenous to oral antibiotics in clinically stabilized patients could reduce the side effects associated with intravenous treatment and shorten the length of hospital stay. Evidence supporting partial oral therapy as an alternative to the routinely recommended continued parenteral therapy is scarce, although observational data suggest that this strategy may be safe and effective. Study Design This is a noninferiority, multicenter, prospective, randomized, open-label study of partial oral treatment with antibiotics compared with full parenteral treatment in left-sided IE. Stable patients (n = 400) with streptococci, staphylococci, or enterococci infecting the mitral valve or the aortic valve will be included. After a minimum of 10 days of parenteral treatment, stable patients are randomized to oral therapy or unchanged parenteral therapy. Recommendations for oral treatment have been developed based on minimum inhibitory concentrations and pharmacokinetic calculations. Patients will be followed up for 6 months after completion of antibiotic therapy. The primary end point is a composition of all-cause mortality, unplanned cardiac surgery, embolic events, and relapse of positive blood cultures with the primary pathogen. Conclusion The Partial Oral Treatment of Endocarditis study tests the hypothesis that partial oral antibiotic treatment is as efficient and safe as parenteral therapy in left-sided IE. The trial is justified by a review of the literature, by pharmacokinetic calculations, and by our own experience.</abstract><cop>United States</cop><pub>Mosby, Inc</pub><pmid>23351813</pmid><doi>10.1016/j.ahj.2012.11.006</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0002-8703 |
| ispartof | The American heart journal, 2013-02, Vol.165 (2), p.116-122 |
| issn | 0002-8703 1097-6744 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1282515865 |
| source | Elsevier ScienceDirect Journals Complete - AutoHoldings; MEDLINE; ProQuest Central UK/Ireland |
| subjects | Administration, Oral Adult Aged Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - pharmacokinetics Antibiotics Blood Cardiovascular Dose-Response Relationship, Drug Drug therapy Electrodes Endocarditis, Bacterial - blood Endocarditis, Bacterial - drug therapy Female Follow-Up Studies Heart Heart surgery Hospitalization Humans Injections, Intravenous Male Middle Aged Mortality Prospective Studies Prostheses Quality of life Studies Success Treatment Outcome |
| title | Partial oral treatment of endocarditis |
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