Improving the clinical accuracy and flexibility of the Alkaptonuria severity score index
Abstract Alkaptonuria (AKU) is a rare genetic disorder where oxidised homogentisic acid accumulates in connective tissues, leading to multisystem disease. The clinical evaluation Alkaptonuria Severity Score Index (cAKUSSI) is a composite score that assesses the extent of AKU disease. However, some c...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-07-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12290 |
| _version_ | 1828775514489225216 |
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| author | Harriet E. O. Cant Iro Chatzidaki Birgitta Olsson Mattias Rudebeck Jean‐Baptiste Arnoux Richard Imrich Lucy A. Eddowes Lakshminarayan R. Ranganath |
| author_facet | Harriet E. O. Cant Iro Chatzidaki Birgitta Olsson Mattias Rudebeck Jean‐Baptiste Arnoux Richard Imrich Lucy A. Eddowes Lakshminarayan R. Ranganath |
| author_sort | Harriet E. O. Cant |
| collection | DOAJ |
| description | Abstract Alkaptonuria (AKU) is a rare genetic disorder where oxidised homogentisic acid accumulates in connective tissues, leading to multisystem disease. The clinical evaluation Alkaptonuria Severity Score Index (cAKUSSI) is a composite score that assesses the extent of AKU disease. However, some components assess similar disease features, are difficult to measure reliably or cannot be measured in resource‐limited environments. cAKUSSI data from the 4‐year SONIA 2 randomised controlled trial, which investigated nitisinone treatment in adults with AKU, were analysed (N = 125). Potentially biased or low‐information cAKUSSI measurements were identified using clinical and statistical input to create a revised AKUSSI for use in AKU research (cAKUSSI 2.0). Additionally, resource‐intensive measurements were removed to explore a flexible AKUSSI (flex‐AKUSSI) for use in low‐resource environments. Revised scores were compared to cAKUSSI in terms of correlation and how they capture disease progression and treatment response. Eight measurements were removed from the cAKUSSI to create the cAKUSSI 2.0, which performed comparably to the cAKUSSI in measuring disease extent, progression and treatment response. When removing resource‐intensive measurements except for osteoarticular disease, the flex‐AKUSSI was highly correlated with the cAKUSSI, indicating that they quantified disease extent similarly. However, when osteoarticular disease (measured using scans) was removed, the corresponding flex‐AKUSSI underestimated disease progression and overestimated treatment response compared to the cAKUSSI. Clinicians may use the cAKUSSI 2.0 to reduce time, effort and patient burden. Clinicians in resource‐limited environments may find value in computing a flex‐AKUSSI score, offering potential for future global registries to expand knowledge about AKU. |
| first_indexed | 2024-12-11T15:41:38Z |
| format | Article |
| id | doaj.art-bd9d7265c2564712ae3e74349d93a2bd |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-12-11T15:41:38Z |
| publishDate | 2022-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-bd9d7265c2564712ae3e74349d93a2bd2022-12-22T00:59:48ZengWileyJIMD Reports2192-83122022-07-0163436137010.1002/jmd2.12290Improving the clinical accuracy and flexibility of the Alkaptonuria severity score indexHarriet E. O. Cant0Iro Chatzidaki1Birgitta Olsson2Mattias Rudebeck3Jean‐Baptiste Arnoux4Richard Imrich5Lucy A. Eddowes6Lakshminarayan R. Ranganath7Costello Medical London UKCostello Medical London UKGarriguella AB Ekerö SwedenOnPoint Science AB Stockholm SwedenHôpital Necker‐Enfants Malades Paris FranceInstitute of Clinical and Translational Research Biomedical Research Centre, Slovak Academy of Sciences Bratislava SlovakiaCostello Medical London UKDepartment of Clinical Biochemistry and Metabolic Medicine Liverpool University Hospitals NHS Foundation Trust Liverpool UKAbstract Alkaptonuria (AKU) is a rare genetic disorder where oxidised homogentisic acid accumulates in connective tissues, leading to multisystem disease. The clinical evaluation Alkaptonuria Severity Score Index (cAKUSSI) is a composite score that assesses the extent of AKU disease. However, some components assess similar disease features, are difficult to measure reliably or cannot be measured in resource‐limited environments. cAKUSSI data from the 4‐year SONIA 2 randomised controlled trial, which investigated nitisinone treatment in adults with AKU, were analysed (N = 125). Potentially biased or low‐information cAKUSSI measurements were identified using clinical and statistical input to create a revised AKUSSI for use in AKU research (cAKUSSI 2.0). Additionally, resource‐intensive measurements were removed to explore a flexible AKUSSI (flex‐AKUSSI) for use in low‐resource environments. Revised scores were compared to cAKUSSI in terms of correlation and how they capture disease progression and treatment response. Eight measurements were removed from the cAKUSSI to create the cAKUSSI 2.0, which performed comparably to the cAKUSSI in measuring disease extent, progression and treatment response. When removing resource‐intensive measurements except for osteoarticular disease, the flex‐AKUSSI was highly correlated with the cAKUSSI, indicating that they quantified disease extent similarly. However, when osteoarticular disease (measured using scans) was removed, the corresponding flex‐AKUSSI underestimated disease progression and overestimated treatment response compared to the cAKUSSI. Clinicians may use the cAKUSSI 2.0 to reduce time, effort and patient burden. Clinicians in resource‐limited environments may find value in computing a flex‐AKUSSI score, offering potential for future global registries to expand knowledge about AKU.https://doi.org/10.1002/jmd2.12290Alkaptonuriacomposite measuredisease progressionnitisinoneresource‐limited |
| spellingShingle | Harriet E. O. Cant Iro Chatzidaki Birgitta Olsson Mattias Rudebeck Jean‐Baptiste Arnoux Richard Imrich Lucy A. Eddowes Lakshminarayan R. Ranganath Improving the clinical accuracy and flexibility of the Alkaptonuria severity score index JIMD Reports Alkaptonuria composite measure disease progression nitisinone resource‐limited |
| title | Improving the clinical accuracy and flexibility of the Alkaptonuria severity score index |
| title_full | Improving the clinical accuracy and flexibility of the Alkaptonuria severity score index |
| title_fullStr | Improving the clinical accuracy and flexibility of the Alkaptonuria severity score index |
| title_full_unstemmed | Improving the clinical accuracy and flexibility of the Alkaptonuria severity score index |
| title_short | Improving the clinical accuracy and flexibility of the Alkaptonuria severity score index |
| title_sort | improving the clinical accuracy and flexibility of the alkaptonuria severity score index |
| topic | Alkaptonuria composite measure disease progression nitisinone resource‐limited |
| url | https://doi.org/10.1002/jmd2.12290 |
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