dc.contributor.author | Stalund, Ida Viken | |
dc.date.accessioned | 2023-09-29T10:41:11Z | |
dc.date.available | 2023-09-29T10:41:11Z | |
dc.date.issued | 2023-10-13 | |
dc.date.submitted | 2023-09-27T15:03:57.993Z | |
dc.identifier | container/6a/10/24/8b/6a10248b-7d38-4400-a2ff-892a0787aa61 | |
dc.identifier.isbn | 9788230859650 | |
dc.identifier.isbn | 9788230850336 | |
dc.identifier.uri | https://hdl.handle.net/11250/3093046 | |
dc.description.abstract | Bakgrunn og målsetting: Polymeren polyvinylpyrrolidon (PVP) er mye brukt som tilsetningsstoff i legemidler. PVP med høy molekylvekt kan ikke utskilles via nyrene og vil derfor opphopes i kroppens vev dersom det administreres parenteralt. I 2013 oppdaget patologer ved Haukeland universitetssykehus tilfeller av PVP-avleiring i vevsprøver fra pasienter med opioidavhengighet og intravenøs rusbruk. En av legemidlene som på den tiden ble brukt i legemiddelassistert rehabilitering (LAR) var en metadonsirup ment for oral bruk som inneholdt PVP med svært høy molekylvekt (PVP K90). Man mistenkte at intravenøs bruk av denne metadonsirupen var årsaken til PVP-avleiring hos pasientene. Denne oppdagelsen førte til at metadonsirupen ble trukket fra markedet i Norge og i EU, og var utgangspunktet for prosjektet som denne doktorgraden er basert på. Hovedmålsettingen for doktorgraden var å studere de patologiske funnene hos pasienter med PVP avleiringssykdom etter injeksjon av PVP-holdige legemidler for opioidsubstitusjon og å vurdere de kliniske konsekvensene.
Metoder: Studiene baserer seg i hovedsak på grundig kvalitativ og kvantitativ evaluering av vevsprøver tatt i diagnostisk øyemed og ved obduksjoner samt vurdering av de patologiske funnene opp mot kliniske data.
Resultater: Denne graden handler om de patologiske og kliniske funnene i 33 pasienter med PVP-avleiringssykdom. Alle biopsier og obduksjonsprøver viste PVP-avleiringer som i noen tilfeller var svært utbredt. Funnene tyder sterkt på at PVP-avleiring har forårsaket alvorlig anemi, patologiske beinbrudd og kronisk nyresykdom. Hos to pasienter forårsaket PVP-avleiringer sannsynligvis dødelig utfall.
Konklusjon: Intravenøs bruk av en metadonsirup som var ment for oral bruk, og som inneholdt PVP K90 som tilsetningsstoff, har forårsaket PVP-avleiringer hos ruspasienter. I noen tilfeller er det sannsynlig at dette har forårsaket alvorlig sykdom og død. Denne graden fremhever viktigheten av en grundig patologisk evaluering av vevsprøver og den viser hvordan melding om mulige bivirkninger, selv fra patologer, kan utgjøre en stor forskjell for pasientene. Den viser også hvordan velmente forsøk på å hindre uønsket bruk av medisiner kan få uønskede konsekvenser. | en_US |
dc.description.abstract | Background and aims: The polymer polyvinylpyrrolidone (PVP) is commonly used as an excipient in drugs. Parenterally administered high molecular weight PVP cannot be excreted, and therefore accumulates in tissues, resulting in PVP deposition. In 2013, pathologists at Haukeland University Hospital discovered cases of PVP deposition in tissue samples from patients with opioid addiction and intravenous drug use (IVDU), most of whom were enrolled in the opioid substitution therapy (OST) program in Norway. Intravenous injection of a specific opioid substitution drug, an oral methadone syrup containing very high molecular weight PVP (PVP K90) was the suspected cause of PVP deposition in these patients. This discovery eventually led to the withdrawal of this methadone syrup from the market in Norway and the European Union (EU) and was the origin of the project on which this thesis is based. The main objective of this thesis was to study the pathological findings in patients with PVP deposition disease from injection of PVP-containing opioid substitution drugs and to assess the clinical consequences.
Methods: The principal methods used in the studies were thorough qualitative and quantitative evaluations of histological specimens collected for diagnostic purposes and at autopsies. The pathological findings were then correlated with clinical data.
Results: This thesis discusses the pathological and clinical findings of 33 patients with PVP deposition. All biopsies and autopsy samples revealed PVP deposits, and in some patients, PVP deposition was very extensive. The findings strongly indicate that PVP deposition has caused severe anemia, pathological fractures and chronic kidney disease. In two patients, PVP deposition likely caused the fatal outcome.
Conclusions: Intravenous use of an oral methadone syrup containing PVP K90 has led to PVP deposition in patients with opioid addiction and IVDU, in some patients likely resulting in severe disease and fatal outcome. This thesis underscores the importance of a thorough pathological investigation of tissue samples and shows how reporting potential adverse drug reactions, even by pathologists, can make a big difference for patients. It also shows how well intended efforts to prevent unintended uses of drugs can have unwanted consequences. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | The University of Bergen | en_US |
dc.relation.haspart | Paper I: Ida Viken Stalund, Gro Nygard Riise, Friedemann Leh, Tormod Karlsen Bjånes, Lars Riise, Einar Svarstad and Sabine Leh. Case Report: Polyvinylpyrrolidone deposition disease from repeated injection of opioid substitution drugs: report of a case with a fatal outcome. F1000Research 2021, 10:300. The article is available at: <a href="https://hdl.handle.net/11250/2831256" target="blank">https://hdl.handle.net/11250/2831256</a> | en_US |
dc.relation.haspart | Paper II: Friedemann Leh, Ida Viken Stalund, Tormod Karlsen Bjånes, Christian Ohldieck, Einar Svarstad and Sabine Leh. Polyvinylpyrrolidone deposition disease in patients with intravenous opioid use: a case series. Human Pathology, 2021 Jul 28;116:102- 111. The article is available at: <a href="https://hdl.handle.net/11250/2834378" target="blank">https://hdl.handle.net/11250/2834378</a> | en_US |
dc.relation.haspart | Paper III: Ida V. Stalund, Heidi Grønseth, Finn P. Reinholt, Einar Svarstad, Hans-Peter Marti and Sabine Leh. Chronic Kidney Disease from Polyvinylpyrrolidone Deposition in Persons with Intravenous Drug Use. CJASN April 2022, 17 (4) 518-526. The published version is not available in BORA due to publisher restrictions. The accepted version is available at: <a href="https://hdl.handle.net/11250/3063816" target="blank">https://hdl.handle.net/11250/3063816</a> | en_US |
dc.rights | Attribution (CC BY). This item's rights statement or license does not apply to the included articles in the thesis. | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | Polyvinylpyrrolidone deposition disease : The role of pathology in understanding disease and death in persons with opioid addiction and intravenous drug use | en_US |
dc.type | Doctoral thesis | en_US |
dc.date.updated | 2023-09-27T15:03:57.993Z | |
dc.rights.holder | Copyright the Author. | en_US |
dc.contributor.orcid | https://orcid.org/0000-0002-2466-355X | |
dc.description.degree | Doktorgradsavhandling | |
fs.unitcode | 13-24-0 | |