{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:27:33Z","timestamp":1789687653428,"version":"4.0.1"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol Toxicol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hyponatremia, a marker of disease severity and prognosis, has been associated with various clinical factors and drug use, especially diuretics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This observational prospective cohort study enrolled patients hospitalized at the University Hospital Center Split because of heart failure (HF). We investigated the association of clinical variables and cardiovascular drugs, including furosemide, hydrochlorothiazide, spironolactone, and their doses, with the presence of hyponatremia at admission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 565 included patients, 32.4% were hyponatremic, 62.6% were males, and the mean age was 73.1\u2009\u00b1\u200910.6\u2009years. In the univariate analysis, hyponatremic patients were more often current smokers (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01), alcohol consumers (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01), receiving spironolactone (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004) or combination of furosemide and spironolactone (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003). Patients who received 50 and 100\u2009mg of spironolactone, compared to those receiving 25\u2009mg (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001), as well as patients who received 250 to 500\u2009mg of furosemide compared to \u2264240\u2009mg (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001), were significantly more often hyponatremic. In the multivariate analysis, when diuretic doses were accounted for, furosemide doses of 250 to 500\u2009mg (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009), spironolactone doses of 50 to 100\u2009mg (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0003), increasing age (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03), diabetes mellitus (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.02) and alcohol consumption (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04) were independently associated with hyponatremia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>High doses of furosemide and spironolactone, or concomitant use of these diuretics, seem to be an important cause of hyponatremia in HF patients, particularly in combination with advanced age, diabetes and alcohol consumption. Diuretic dose reduction may help avoid hyponatremia and improve clinical status and prognosis in such patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40360-020-00431-4","type":"journal-article","created":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T12:05:10Z","timestamp":1598357110000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Furosemide and spironolactone doses and hyponatremia in patients with heart failure"],"prefix":"10.1186","volume":"21","author":[{"given":"Ivan","family":"Velat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017deljko","family":"Bu\u0161i\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Juri\u0107 Pai\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktor","family":"\u010culi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"issue":"9","key":"431_CR1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.4330\/wjc.v5.i9.317","volume":"5","author":"TD Filippatos","year":"2013","unstructured":"Filippatos TD, Elisaf MS. Hyponatremia in patients with heart failure. World J Cardiol. 2013;5(9):317\u201328.","journal-title":"World J Cardiol"},{"issue":"4","key":"431_CR2","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/s10741-015-9482-y","volume":"20","author":"C Urso","year":"2015","unstructured":"Urso C, Brucculeri S, Caimi G. Acid-base and electrolyte abnormalities in heart failure: pathophysiology and implications. Heart Fail Rev. 2015;20(4):493\u2013503.","journal-title":"Heart Fail Rev"},{"issue":"2","key":"431_CR3","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1388-9842(01)00234-3","volume":"4","author":"HJ Milionis","year":"2002","unstructured":"Milionis HJ, Alexandrides GE, Liberopoulos EN, Bairaktari ET, Goudevenos J, Elisaf MS. Hypomagnesemia and concurrent acid-base and electrolyte abnormalities in patients with congestive heart failure. Eur J Heart Fail. 2002;4(2):167\u201373.","journal-title":"Eur J Heart Fail"},{"key":"431_CR4","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.2147\/CIA.S138535","volume":"12","author":"TD Filippatos","year":"2017","unstructured":"Filippatos TD, Makri A, Elisaf MS, Liamis G. Hyponatremia in the elderly: challenges and solutions. Clin Interv Aging. 2017;12:1957\u201365.","journal-title":"Clin Interv Aging"},{"issue":"Suppl","key":"431_CR5","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/imj.13682","volume":"48","author":"M Woodward","year":"2018","unstructured":"Woodward M, Gonski P, Grossmann M, Obeid J, Scholes R, Topliss DJ. Diagnosis and management of hyponatraemia in the older patient. Intern Med J. 2018;48(Suppl):5\u201312.","journal-title":"Intern Med J"},{"issue":"1","key":"431_CR6","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nrneph.2012.246","volume":"9","author":"RW Schrier","year":"2013","unstructured":"Schrier RW, Sharma S, Shchekochikhin D. Hyponatraemia: more than just a marker of disease severity? Nat Rev Nephrol. 2013;9(1):37\u201350.","journal-title":"Nat Rev Nephrol"},{"issue":"10","key":"431_CR7","doi-asserted-by":"crossref","first-page":"488","DOI":"10.12998\/wjcc.v2.i10.488","volume":"2","author":"G Liamis","year":"2014","unstructured":"Liamis G, Liberopoulos E, Barkas F, Elisaf M. Diabetes mellitus and electrolyte disorders. World J Clin Cases. 2014;2(10):488\u201396.","journal-title":"World J Clin Cases"},{"issue":"6","key":"431_CR8","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1056\/NEJMra1503102","volume":"373","author":"BF Palmer","year":"2015","unstructured":"Palmer BF, Clegg DJ. Electrolyte and Acid-Base disturbances in patients with diabetes mellitus. N Engl J Med. 2015;373(6):548\u201359.","journal-title":"N Engl J Med"},{"key":"431_CR9","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2147\/IJGM.S110872","volume":"9","author":"K Ali","year":"2016","unstructured":"Ali K, Workicho A, Gudina EK. Hyponatremia in patients hospitalized with heart failure: a condition often overlooked in low-income settings. Int J Gen Med. 2016;9:267\u201373.","journal-title":"Int J Gen Med"},{"issue":"11","key":"431_CR10","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1016\/j.amjcard.2014.03.017","volume":"113","author":"C Bavishi","year":"2014","unstructured":"Bavishi C, Ather S, Bambhroliya A, Jneid H, Virani SS, Bozkurt B, et al. Prognostic significance of hyponatremia among ambulatory patients with heart failure and preserved and reduced ejection fractions. Am J Cardiol. 2014;113(11):1834\u20138.","journal-title":"Am J Cardiol"},{"issue":"14","key":"431_CR11","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1056\/NEJMra1704724","volume":"377","author":"BF Palmer","year":"2017","unstructured":"Palmer BF, Clegg DJ. Electrolyte disturbances in patients with chronic alcohol-use disorder. N Engl J Med. 2017;377(14):1368\u201377.","journal-title":"N Engl J Med"},{"issue":"3","key":"431_CR12","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.amjmed.2012.06.037","volume":"126","author":"G Liamis","year":"2013","unstructured":"Liamis G, Rodenburg EM, Hofman A, Zietse R, Stricker BH, Hoorn EJ. Electrolyte disorders in community subjects: prevalence and risk factors. Am J Med. 2013;126(3):256\u201363.","journal-title":"Am J Med"},{"issue":"1","key":"431_CR13","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1053\/j.ajkd.2008.03.004","volume":"52","author":"G Liamis","year":"2008","unstructured":"Liamis G, Milionis H, Elisaf M. A review of drug-induced hyponatremia. Am J Kidney Dis. 2008;52(1):144\u201353.","journal-title":"Am J Kidney Dis"},{"key":"431_CR14","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/1741-7015-11-83","volume":"11","author":"S Arampatzis","year":"2013","unstructured":"Arampatzis S, Funk GC, Leichtle AB, Fiedler GM, Schwarz C, Zimmermann H, et al. Impact of diuretic therapy-associated electrolyte disorders present on admission to the emergency department: a cross-sectional analysis. BMC Med. 2013;11:83.","journal-title":"BMC Med"},{"issue":"5","key":"431_CR15","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2015-009775","volume":"6","author":"H Nankabirwa","year":"2016","unstructured":"Nankabirwa H, Kalyesubula R, Ssinabulya I, Katabira ET, Cumming RG. A cross-sectional study of hyponatraemia among elderly patients with heart failure in Uganda. BMJ Open. 2016;6(5):e009775.","journal-title":"BMJ Open"},{"issue":"9A","key":"431_CR16","doi-asserted-by":"crossref","first-page":"2B","DOI":"10.1016\/j.amjcard.2005.03.002","volume":"95","author":"RM Oren","year":"2005","unstructured":"Oren RM. Hyponatremia in congestive heart failure. Am J Cardiol. 2005;95(9A):2B\u20137B.","journal-title":"Am J Cardiol"},{"issue":"5","key":"431_CR17","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1517\/14656566.2014.879117","volume":"15","author":"J Tamargo","year":"2014","unstructured":"Tamargo J, Segura J, Ruilope LM. Diuretics in the treatment of hypertension. Part 2: loop diuretics and potassium-sparing agents. Expert Opin Pharmacother. 2014;15(5):605\u201321.","journal-title":"Expert Opin Pharmacother"},{"issue":"816","key":"431_CR18","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1136\/pgmj.69.816.797","volume":"69","author":"HM Fidler","year":"1993","unstructured":"Fidler HM, Goldman J, Bielawska CA, Rai GS, Hoffbrand BI. A study of plasma sodium levels in elderly people taking amiloride or triamterene in combination with hydrochlorothiazide. Postgrad Med J. 1993;69(816):797\u20139.","journal-title":"Postgrad Med J"},{"issue":"6","key":"431_CR19","doi-asserted-by":"crossref","first-page":"461","DOI":"10.7326\/0003-4819-130-6-199903160-00002","volume":"130","author":"AS Levey","year":"1999","unstructured":"Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med. 1999;130(6):461\u201370.","journal-title":"Ann Intern Med"},{"issue":"2","key":"431_CR20","first-page":"315","volume":"118","author":"II Costache","year":"2014","unstructured":"Costache II, Alexandrescu DM, Cimpoe\u015fu D, Petri\u015f OR, Petri\u015f AO. Hyponatremia--risk factor in patients with chronic heart failure--clinical, evolutive and therapeutic implications. Rev Med Chir Soc Med Nat Iasi. 2014;118(2):315\u20139.","journal-title":"Rev Med Chir Soc Med Nat Iasi"},{"issue":"11","key":"431_CR21","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1093\/ndt\/gfi109","volume":"20","author":"P Gross","year":"2005","unstructured":"Gross P, Palm C. Thiazides: do they kill? Nephrol Dial Transplant. 2005;20(11):2299\u2013301.","journal-title":"Nephrol Dial Transplant"},{"issue":"4","key":"431_CR22","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1111\/j.1365-2265.2005.02318.x","volume":"63","author":"RM Reynolds","year":"2005","unstructured":"Reynolds RM, Seckl JR. Hyponatraemia for the clinical endocrinologist. Clin Endocrinol. 2005;63(4):366\u201374.","journal-title":"Clin Endocrinol"},{"issue":"8","key":"431_CR23","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1093\/eurheartj\/ehl542","volume":"28","author":"M Gheorghiade","year":"2007","unstructured":"Gheorghiade M, Abraham WT, Albert NM, Gattis Stough W, Greenberg BH, O\u2019Connor CM, et al. Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry. Eur Heart J. 2007;28(8):980\u20138.","journal-title":"Eur Heart J"},{"issue":"19","key":"431_CR24","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1001\/jama.290.19.2581","volume":"290","author":"DS Lee","year":"2003","unstructured":"Lee DS, Austin PC, Rouleau JL, Liu PP, Naimark D, Tu JV. Predicting mortality among patients hospitalized for heart failure: derivation and validation of a clinical model. JAMA. 2003;290(19):2581\u20137.","journal-title":"JAMA"},{"issue":"18","key":"431_CR25","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1056\/NEJM199511023331806","volume":"333","author":"MW Rich","year":"1995","unstructured":"Rich MW, Beckham V, Wittenberg C, Leven CL, Freedland KE, Carney RM. A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med. 1995;333(18):1190\u20135.","journal-title":"N Engl J Med"},{"issue":"5","key":"431_CR26","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/S0953-6205(02)00086-9","volume":"13","author":"PS Wong","year":"2002","unstructured":"Wong PS, Davidsson GK, Timeyin J, Warren A, Watson DJ, Vincent R, et al. Heart failure in patients admitted to hospital: mortality is still high. Eur J Intern Med. 2002;13(5):304\u201310.","journal-title":"Eur J Intern Med"},{"key":"431_CR27","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.ijcard.2017.08.004","volume":"248","author":"JJ Park","year":"2017","unstructured":"Park JJ, Cho YJ, Oh IY, Park HA, Lee HY, Kim KH, et al. Short and long-term prognostic value of hyponatremia in heart failure with preserved ejection fraction versus reduced ejection fraction. An analysis of the Korean acute heart failure registry. Int J Cardiol. 2017;248:239\u201345.","journal-title":"Int J Cardiol"},{"issue":"9","key":"431_CR28","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/j.cjca.2019.04.002","volume":"35","author":"H Yogasundaram","year":"2019","unstructured":"Yogasundaram H, Chappell MC, Braam B, Oudit GY. Cardiorenal syndrome and heart failure\u2014challenges and opportunities. Can J Cardiol. 2019;35(9):1208\u201319.","journal-title":"Can J Cardiol"},{"issue":"12","key":"431_CR29","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1093\/qjmed\/hcg157","volume":"96","author":"KM Chow","year":"2003","unstructured":"Chow KM, Szeto CC, Wong TY, Leung CB, Li PK. Risk factors for thiazide-induced hyponatraemia. QJM. 2003;96(12):911\u20137.","journal-title":"QJM"},{"issue":"10","key":"431_CR30","first-page":"1305","volume":"96","author":"KM Chow","year":"2004","unstructured":"Chow KM, Kwan BC, Szeto CC. Clinical studies of thiazide-induced hyponatremia. J Natl Med Assoc. 2004;96(10):1305\u20138.","journal-title":"J Natl Med Assoc"},{"issue":"9","key":"431_CR31","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/j.1751-7176.2012.00673.x","volume":"14","author":"DL Cohen","year":"2012","unstructured":"Cohen DL, Townsend RR. Hyponatremia and thiazides. J Clin Hypertens. 2012;14(9):653.","journal-title":"J Clin Hypertens"},{"key":"431_CR32","doi-asserted-by":"publisher","unstructured":"Kanchanasurakit S, Saokaew S, Siriplabpla W, Arsu A, Boonmak W, Watcharasiriphong W. Development of a hyponatremia screening tool (ABCDF-S score) for patients with hypertension using thiazide diuretic agents. J Clin Pharm Ther. 2020. https:\/\/doi.org\/10.1111\/jcpt.13123 [Epub ahead of print].","DOI":"10.1111\/jcpt.13123"},{"issue":"10","key":"431_CR33","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1093\/eurjhf\/hfs115","volume":"14","author":"N Deubner","year":"2012","unstructured":"Deubner N, Berliner D, Frey A, G\u00fcder G, Brenner S, Fenske W, et al. Dysnatraemia in heart failure. Eur J Heart Fail. 2012;14(10):1147\u201354.","journal-title":"Eur J Heart Fail"},{"issue":"3","key":"431_CR34","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/ejhf.462","volume":"18","author":"K Damman","year":"2016","unstructured":"Damman K, Kjekshus J, Wikstrand J, Cleland JG, Komajda M, Wedel H, et al. Loop diuretics, renal function and clinical outcome in patients with heart failure and reduced ejection fraction. Eur J Heart Fail. 2016;18(3):328\u201336.","journal-title":"Eur J Heart Fail"},{"issue":"6","key":"431_CR35","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.jchf.2014.05.014","volume":"2","author":"PM McKie","year":"2014","unstructured":"McKie PM, Schirger JA, Benike SL, Harstad LK, Chen HH. The effects of dose reduction of furosemide on glomerular filtration rate in stable systolic heart failure. JACC Heart Fail. 2014;2(6):675\u20137.","journal-title":"JACC Heart Fail"},{"issue":"2","key":"431_CR36","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.ijcard.2014.09.156","volume":"177","author":"CJ Kapelios","year":"2014","unstructured":"Kapelios CJ, Kaldara E, Ntalianis A, Nana E, Pantsios C, Repasos E, et al. Lowering furosemide dose in stable chronic heart failure patients with reduced ejection fraction is not accompanied by decompensation: a randomized study. Int J Cardiol. 2014;177(2):690\u20132.","journal-title":"Int J Cardiol"},{"issue":"8","key":"431_CR37","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1111\/j.1445-5994.2010.02217.x","volume":"40","author":"DS Shapiro","year":"2010","unstructured":"Shapiro DS, Sonnenblick M, Galperin I, Melkonyan L, Munter G. Severe hyponatraemia in elderly hospitalized patients: prevalence, aetiology and outcome. Intern Med J. 2010;40(8):574\u201380.","journal-title":"Intern Med J"},{"issue":"7","key":"431_CR38","first-page":"859","volume":"168","author":"JL Chiasson","year":"2003","unstructured":"Chiasson JL, Aris-Jilwan N, B\u00e9langer R, Bertrand S, Beauregard H, Eko\u00e9 JM, et al. Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state. CMAJ. 2003;168(7):859\u201366.","journal-title":"CMAJ"},{"issue":"11","key":"431_CR39","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1345\/aph.1D105","volume":"37","author":"BF Palmer","year":"2003","unstructured":"Palmer BF, Gates JR, Lader M. Causes and management of hyponatremia. Ann Pharmacother. 2003;37(11):1694\u2013702.","journal-title":"Ann Pharmacother"},{"issue":"1","key":"431_CR40","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1159\/000351804","volume":"38","author":"G Liamis","year":"2013","unstructured":"Liamis G, Liberopoulos E, Barkas F, Elisaf M. Spurious electrolyte disorders: a diagnostic challenge for clinicians. Am J Nephrol. 2013;38(1):50\u20137.","journal-title":"Am J Nephrol"},{"issue":"2","key":"431_CR41","doi-asserted-by":"crossref","first-page":"102","DOI":"10.15420\/cfr.2015.1.2.102","volume":"1","author":"N Wettersten","year":"2015","unstructured":"Wettersten N, Maisel A. Role of cardiac troponin levels in acute heart failure. Card Fail Rev. 2015;1(2):102\u20136.","journal-title":"Card Fail Rev"},{"key":"431_CR42","doi-asserted-by":"crossref","unstructured":"Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, et al. ACCF\/AHA guideline for the Management of Heart Failure. Circulation. 2013;2013, 128(16).","DOI":"10.1161\/CIR.0b013e31829e8776"},{"issue":"2","key":"431_CR43","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/ejhf.1369","volume":"21","author":"W Mullens","year":"2019","unstructured":"Mullens W, Damman K, Harjola VP, Mebazaa A, Brunner-La Rocca HP, Martens P, et al. The use of diuretics in heart failure with congestion - a position statement from the heart failure Association of the European Society of cardiology. Eur J Heart Fail. 2019;21(2):137\u201355.","journal-title":"Eur J Heart Fail"}],"container-title":["BMC Pharmacology and Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-020-00431-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40360-020-00431-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40360-020-00431-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,2]],"date-time":"2021-08-02T19:37:55Z","timestamp":1627933075000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcpharmacoltoxicol.biomedcentral.com\/articles\/10.1186\/s40360-020-00431-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,3]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["431"],"URL":"https:\/\/doi.org\/10.1186\/s40360-020-00431-4","relation":{},"ISSN":["2050-6511"],"issn-type":[{"value":"2050-6511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,3]]},"assertion":[{"value":"1 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 July 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study protocol was approved by the Ethics Committee of the University Hospital Center Split (Number 2181\u2013147-01\/06\/M.B.-16\u20132) and all patients gave their written informed consent for participation.","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":"The authors declare they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"57"}}