{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T17:25:38Z","timestamp":1793381138284,"version":"4.5.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T00:00:00Z","timestamp":1573516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T00:00:00Z","timestamp":1573516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Wilson disease (WD) is genetically induced failure of copper metabolism which can be successfully treated with pharmacological agents. The prognosis for survival in most WD patients is favorable if diagnosis and anti-copper treatment are provided early. Many observations imply that persistence with drug treatment is generally low in patients with chronic diseases, which impact the treatment effectiveness, but such results are very limited in WD. The aim of our study was to assess persistence with treatment among WD patients, to analyze its effect on patient outcome and to identify factors that might be related to persistence.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>170 newly diagnosed, symptomatic patients with WD who started treatment between 1995 and 2005 were analyzed retrospectively to assess treatment non-persistence, which was defined as at least one reported break of more than 3\u2009months or minimum two breaks lasting longer than 2\u2009months. Results were further analyzed according to selected clinical variables.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Only 74.1% of patients were persistent with treatment during the mean 11.7\u2009years of follow up. Treatment persistence closely impacted positive clinical outcomes. In patients classified as persistent, improvement and lack of WD progression were observed more often compared to those classified as non-persistent (29.4 and 68.3% vs. 2.3 and 45.5%; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, respectively). In contrast, non-persistent patients presented more often with worsening WD than persistent patients (52.3% vs. 2.4%). Type of WD treatment, gender, phenotypic presentation, adverse events and duration of treatment were not related to treatment persistence. Higher or upper\/post-secondary education and a supportive family attitude towards treatment were the most important factors related to persistence.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>One quarter of WD patients were not taking anti-copper treatment regularly and this had an important negative effect on clinical outcome. Family support played an important role in treatment persistence.<\/jats:p>\n<\/jats:sec>","DOI":"10.1186\/s12883-019-1502-4","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T08:03:18Z","timestamp":1573545798000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Persistence with treatment for Wilson disease: a retrospective study"],"prefix":"10.1186","volume":"19","author":[{"given":"Wojciech","family":"Mase\u0142bas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1956-1866","authenticated-orcid":false,"given":"Anna","family":"Cz\u0142onkowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Litwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maciej","family":"Niewada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,11,12]]},"reference":[{"key":"1502_CR1","doi-asserted-by":"publisher","first-page":"2089","DOI":"10.1002\/hep.22261","volume":"47","author":"EA Roberts","year":"2008","unstructured":"Roberts EA, Schilsky ML. Diagnosis and treatment of Wilson\u2019s disease: an update. Hepatology. 2008;47:2089\u2013111.","journal-title":"Hepatology"},{"key":"1502_CR2","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41572-018-0018-3","volume":"4","author":"A Cz\u0142onkowska","year":"2018","unstructured":"Cz\u0142onkowska A, Litwin T, Dusek P, Ferenci P, Lutsenko S, Medici V, Rybakowski JK, Weiss KH, Schilsky ML. Wilson disease. Nat Rev Dis Primers. 2018;4:21.","journal-title":"Nat Rev Dis Primers"},{"key":"1502_CR3","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1016\/j.jhep.2011.11.007","volume":"56","author":"European Association for Study of Liver","year":"2012","unstructured":"European Association for Study of Liver. EASL clinical practice guidelines: Wilson\u2019s disease. J Hepatol. 2012;56:671\u201385.","journal-title":"J Hepatol"},{"key":"1502_CR4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/0022-510X(93)90145-O","volume":"117","author":"NS Chu","year":"1993","unstructured":"Chu NS, Hung TP. Geographic variations in Wilson\u2019s disease. J Neurol Sci. 1993;117:1\u20137.","journal-title":"J Neurol Sci"},{"key":"1502_CR5","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1007\/s00415-005-0720-4","volume":"252","author":"A Czlonkowska","year":"2005","unstructured":"Czlonkowska A, Tarnacka B, Litwin T, Gajda J, Rodo M. Wilson\u2019s disease \u2013 cause of mortality in 164 patients during 1992-2003 observation period. J Neurol. 2005;252:698\u2013703.","journal-title":"J Neurol"},{"key":"1502_CR6","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/nyas.12437","volume":"1315","author":"KH Weiss","year":"2014","unstructured":"Weiss KH, Stremmel W. Clinical considerations for an effective medical therapy in Wilson's disease. Ann N Y Acad Sci. 2014;1315:81\u20135.","journal-title":"Ann N Y Acad Sci"},{"key":"1502_CR7","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1111\/ene.12348","volume":"21","author":"A Cz\u0142onkowska","year":"2014","unstructured":"Cz\u0142onkowska A, Litwin T, Karli\u0144ski M, Dziezyc K, Chabik G, Czerska M. D-penicillamine versus zinc sulfate as first-line therapy for Wilson\u2019s disease. Eur J Neurol. 2014;21:599\u2013606.","journal-title":"Eur J Neurol"},{"key":"1502_CR8","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1001\/archneur.1987.00520170020016","volume":"44","author":"GJ Brewer","year":"1987","unstructured":"Brewer GJ, Terry CA, Aisen AM, Hill GM. Worsening of neurologic syndrome in patients with Wilson\u2019s disease with initial penicillamine therapy. Arch Neurol. 1987;44:490\u20133.","journal-title":"Arch Neurol"},{"key":"1502_CR9","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1046\/j.1525-1497.1998.00053.x","volume":"13","author":"BG Fincke","year":"1998","unstructured":"Fincke BG, Miller DR, Spiro A 3rd. The interaction of patient perception of overmedication with drug compliance and side effects. J Gen Intern Med. 1998;13:182\u20135.","journal-title":"J Gen Intern Med"},{"key":"1502_CR10","doi-asserted-by":"publisher","first-page":"2101","DOI":"10.1001\/archinte.160.14.2101","volume":"160","author":"MR DiMatteo","year":"2000","unstructured":"DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160:2101\u20137.","journal-title":"Arch Intern Med"},{"key":"1502_CR11","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1521\/jaap.2007.35.2.179","volume":"35","author":"E Leeman","year":"2007","unstructured":"Leeman E. The costs of compliance. J Am Acad Psychoanal Dyn Psychiatr. 2007;35:179\u201387.","journal-title":"J Am Acad Psychoanal Dyn Psychiatr"},{"key":"1502_CR12","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1007\/s00228-012-1298-2","volume":"68","author":"V Conti","year":"2012","unstructured":"Conti V, Lora A, Cipriani A, Fortino I, Merlino L, Barbui C. Persistence with pharmacological treatment in the specialist mental healthcare of patients with severe mental disorders. Eur J Clin Pharmacol. 2012;68:1647\u201355.","journal-title":"Eur J Clin Pharmacol"},{"key":"1502_CR13","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1007\/s00228-013-1555-z","volume":"69","author":"M Qvarnstr\u00f6m","year":"2013","unstructured":"Qvarnstr\u00f6m M, Kahan T, Kieler H, Brandt L, Hasselstr\u00f6m J, Bengtsson Bostr\u00f6m K, et al. Persistence to antihypertensive drug treatment in Swedish primary healthcare. Eur J Clin Pharmacol. 2013;69:1955\u201364.","journal-title":"Eur J Clin Pharmacol"},{"key":"1502_CR14","doi-asserted-by":"publisher","first-page":"709","DOI":"10.2147\/PPA.S47577","volume":"7","author":"EA Pyatak","year":"2013","unstructured":"Pyatak EA, Florindez D, Weigensberg MJ. Adherence decision making in the everyday lives of emerging adults with type I diabetes. Patient Prefer Adherence. 2013;7:709\u201318.","journal-title":"Patient Prefer Adherence"},{"key":"1502_CR15","doi-asserted-by":"publisher","first-page":"1495","DOI":"10.1378\/chest.13-0613","volume":"144","author":"M Dieltjens","year":"2013","unstructured":"Dieltjens M, Braem MJ, Vroegop AV, Wouters K, Verbraecken JA, De Backer WA, et al. Objectively measured vs self-reported compliance during oral appliance therapy for sleep-disordered breathing. Chest. 2013;144:1495\u2013502.","journal-title":"Chest"},{"key":"1502_CR16","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/j.1524-4733.2007.00213.x","volume":"11","author":"JA Cramer","year":"2008","unstructured":"Cramer JA, Roy A, Burrell A, Fuldeore MJ, Ollendorf DA, et al. Medication compliance and persistence terminology and definitions. Value Health. 2008;11:44\u20137.","journal-title":"Value Health"},{"key":"1502_CR17","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1111\/ene.12320","volume":"21","author":"K Dziezyc","year":"2014","unstructured":"Dziezyc K, Karlinski M, Litwin T, Cz\u0142onkowska A. Compliant treatment with anti-copper agents prevents clinically overt Wilson\u2019s disease in pre-symptomatic patients. Eur J Neurol. 2014;21:332\u20137.","journal-title":"Eur J Neurol"},{"key":"1502_CR18","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jns.2011.08.028","volume":"312","author":"T Litwin","year":"2012","unstructured":"Litwin T, Gromadzka G, Czlonkowska A. Gender differences in Wilson\u2019s disease. J Neurol Sci. 2012;312:31\u20135.","journal-title":"J Neurol Sci"},{"key":"1502_CR19","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1097\/00005650-198601000-00007","volume":"24","author":"DE Morisky","year":"1986","unstructured":"Morisky DE, Green LW, Levine DM. Concurrent and predictive validity of a self-reported measure of medication adherence. Med Care. 1986;24:67\u201374.","journal-title":"Med Care"},{"key":"1502_CR20","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S0920-9964(99)00130-9","volume":"42","author":"K Thompson","year":"2000","unstructured":"Thompson K, Kulkarni J, Sergejew AA. Reliability and validity of a new Medication Adherence Rating Scale (MARS) for the psychoses. Schizophr Res. 2000;42:241\u20137.","journal-title":"Schizophr Res"},{"issue":"1\u20133","key":"1502_CR21","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.schres.2007.12.470","volume":"100","author":"MJ Byerly","year":"2008","unstructured":"Byerly MJ, Nakonezny PA, Rush AJ. The Brief Adherence Rating Scale (BARS) validated against electronic monitoring in assessing the antipsychotic medication adherence of outpatients with schizophrenia and schizoaffective disorder. Schizophr Res. 2008;100(1\u20133):60\u20139.","journal-title":"Schizophr Res"},{"key":"1502_CR22","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1097\/01.mcg.0000225670.91722.59","volume":"40","author":"V Medici","year":"2006","unstructured":"Medici V, Trevisan CP, D\u2019Inca R, Barollo M, Zancan L, Fagiuoli S, et al. Diagnosis and management of Wilson\u2019s disease: results of a single center experience. J Clin Gastroenterol. 2006;40:936\u201341.","journal-title":"J Clin Gastroenterol"},{"key":"1502_CR23","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S0002-9343(97)00467-1","volume":"102","author":"NH Miller","year":"1997","unstructured":"Miller NH. Compliance with treatment regimens in chronic asymptomatic diseases. Am J Med. 1997;102:43\u20139.","journal-title":"Am J Med"},{"key":"1502_CR24","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/S0028-3843(14)60040-2","volume":"44","author":"W Maselbas","year":"2010","unstructured":"Maselbas W, Chabik G, Czlonkowska A. Persistence with treatment in patients with Wilson disease. Neurol Neurochir Pol. 2010;44:260\u20133.","journal-title":"Neurol Neurochir Pol"},{"key":"1502_CR25","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.revmed.2017.11.010","volume":"39","author":"E Jacquelet","year":"2018","unstructured":"Jacquelet E, Beretti J, De-Tassigny A, Girardot-Tinant N, Wenisch E, Lachaux A, Pheulpin MC, Poujois A, Woimant F. Compliance with treatment in Wilson's disease: on the interest of a multidisciplinary closer follow-up. Rev Med Interne. 2018;39:155\u201360.","journal-title":"Rev Med Interne"},{"key":"1502_CR26","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.parkreldis.2011.12.007","volume":"18","author":"GJ Hou","year":"2012","unstructured":"Hou GJ, Wu LJ, Moore S, Ward C, York M, Atassi F, et al. Assessment of appropriate medication administration for hospitalized patients with Parkinson\u2019s disease. Parkinsonism Relat Disord. 2012;18:377\u201381.","journal-title":"Parkinsonism Relat Disord"},{"issue":"1\u20132","key":"1502_CR27","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.jns.2015.06.010","volume":"355","author":"T Litwin","year":"2015","unstructured":"Litwin T, Dzie\u017cyc K, Karli\u0144ski M, Chabik G, Czepiel W, Cz\u0142onkowska A. Early neurological worsening in patients with Wilson\u2019s disease. J Neurol Sci. 2015;355(1\u20132):162\u20137.","journal-title":"J Neurol Sci"},{"key":"1502_CR28","doi-asserted-by":"publisher","first-page":"161","DOI":"10.5114\/ninp.2013.34397","volume":"47","author":"T Litwin","year":"2013","unstructured":"Litwin T, Czlonkowska A. Wilson disease \u2013 factors affecting clinical presentation. Neurol Neurochir Pol. 2013;47:161\u20139.","journal-title":"Neurol Neurochir Pol"},{"key":"1502_CR29","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s13023-019-1133-2","volume":"14","author":"W Maselbas","year":"2019","unstructured":"Maselbas W, Litwin T, Czlonkowska A. Social and demographic characteristics of a polish cohort with Wilson disease and the impact of treatment persistence. Orphanet J Rare Dis. 2019;14:167.","journal-title":"Orphanet J Rare Dis"},{"key":"1502_CR30","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/BF00868525","volume":"243","author":"A Cz\u0142onkowska","year":"1996","unstructured":"Cz\u0142onkowska A, Gajda J, Rodo M. Effects of long-term treatment in Wilson\u2019s disease with d-penicillamine and zinc sulphate. J Neurol. 1996;243:269\u201373.","journal-title":"J Neurol"},{"key":"1502_CR31","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1007\/s10620-014-3495-6","volume":"60","author":"A Ala","year":"2015","unstructured":"Ala A, Aliu E, Schilsky ML. Prospective pilot study of a single daily dosage of trientine for the treatment of Wilson disease. Dig Dis Sci. 2015;60:1433\u20139.","journal-title":"Dig Dis Sci"},{"key":"1502_CR32","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/S2468-1253(17)30293-5","volume":"2","author":"KH Weiss","year":"2017","unstructured":"Weiss KH, Askari FK, Czlonkowska A, Ferenci P, Bronstein JM, Bega D, Ala A, Nicholl D, Flint S, Olsson L, Plitz T, Bjartmar C, Schilsky ML. Bis-choline tetrathiomolybdate in patients with Wilson's disease: an open-label, multicentre, phase 2 study. Lancet Gastroenterol Hepatol. 2017;2:869\u201376.","journal-title":"Lancet Gastroenterol Hepatol"}],"container-title":["BMC Neurology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-019-1502-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12883-019-1502-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12883-019-1502-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:15:52Z","timestamp":1605053752000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcneurol.biomedcentral.com\/articles\/10.1186\/s12883-019-1502-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,12]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["1502"],"URL":"https:\/\/doi.org\/10.1186\/s12883-019-1502-4","relation":{},"ISSN":["1471-2377"],"issn-type":[{"value":"1471-2377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,12]]},"assertion":[{"value":"9 April 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 November 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The ethics committee at the Institute of Psychiatry and Neurology (Warsaw, Poland) approved the study. All patients gave written informed consent.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"We have no relevant financial interest in the submitted publication matter. All financial involvement (e.g., employment, consultancies, honoraria, stock ownership or options, grants or patents receiving or pending, royalties) with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the submitted publication material are completely disclosed.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"278"}}