{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:26:11Z","timestamp":1791390371075,"version":"4.3.3"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T00:00:00Z","timestamp":1721865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009410","name":"Universitat de Lleida","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009410","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Brain Res"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A higher level of education was correlated with less severe motor impairment in Parkinson\u2019s Disease (PD). Nevertheless, there is limited evidence on the relationship between cognitive reserve and motor performance in complex situations in PD. To investigate the association between cognitive reserve and the dual-task gait effect in PD. Additionally, we examined the relationship between executive function, clinical and sociodemographic variables and, dual-task gait effects. We conducted a cross-sectional study with 44 PD participants. We evaluated dual-task effect on cadence, stride length, and gait velocity. Dual-task effects were correlated with neurophysiological factors, including cognitive reserve (Cognitive Reserve Index Questionnaire), overall cognitive performance of executive functions, a specific executive function domain (Trail Making Test), and the global cognitive status (Montreal Cognitive Assessment and Mini-Mental State Examination). Age, gender, and disease severity were considered as variables to be examined for correlation. We found that cognitive reserve did not influence gait performance under dual-task conditions in this sample. However, executive functions, age, and disease severity were associated with the dual-task effect on gait. The overall cognitive performance with respect to the Trail Making Test showed an inverse relationship in the dual-task gait effect on cadence. Our study\u2019s findings have important implications for understanding the association between executive functions, age, and disease severity with the dual-task effect on gait in PD. Pre-life factors, such as education, occupation, and leisure activity, did not contribute to coping with complex gait situations in PD.<\/jats:p>","DOI":"10.1007\/s00221-024-06897-6","type":"journal-article","created":{"date-parts":[[2024,7,25]],"date-time":"2024-07-25T07:03:04Z","timestamp":1721890984000},"page":"2271-2278","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Cognitive reserve and executive functions in dual task gait performance in Parkinson\u2019s disease"],"prefix":"10.1007","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0772-666X","authenticated-orcid":false,"given":"Helena","family":"Fern\u00e1ndez-Lago","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pere","family":"Bosch-Barcel\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Andr\u00e9s","family":"S\u00e1nchez-Molina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Ambrus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel \u00c1ngel","family":"Fern\u00e1ndez-Del-Olmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,25]]},"reference":[{"issue":"6","key":"6897_CR1","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/J.JCLINEPI.2014.12.014","volume":"68","author":"PC Austin","year":"2015","unstructured":"Austin PC, Steyerberg EW (2015) The number of subjects per variable required in linear regression analyses. J Clin Epidemiol 68(6):627\u2013636. https:\/\/doi.org\/10.1016\/J.JCLINEPI.2014.12.014","journal-title":"J Clin Epidemiol"},{"issue":"1","key":"6897_CR2","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1002\/MDS.27902","volume":"35","author":"C Baiano","year":"2020","unstructured":"Baiano C, Barone P, Trojano L, Santangelo G (2020) Prevalence and clinical aspects of mild cognitive impairment in Parkinson\u2019s disease: a meta-analysis. Mov Disord 35(1):45\u201354. https:\/\/doi.org\/10.1002\/MDS.27902","journal-title":"Mov Disord"},{"key":"6897_CR3","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/J.GAITPOST.2023.11.016","volume":"108","author":"ST Baudendistel","year":"2024","unstructured":"Baudendistel ST, Haussler AM, Rawson KS, Earhart GM (2024) Minimal clinically important differences of Spatiotemporal Gait Variables in Parkinson Disease. Gait Posture 108:257. https:\/\/doi.org\/10.1016\/J.GAITPOST.2023.11.016","journal-title":"Gait Posture"},{"issue":"13","key":"6897_CR4","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1212\/01.wnl.0000306632.43729.24","volume":"70","author":"TC Buter","year":"2008","unstructured":"Buter TC, van den Hout A, Matthews FE, Larsen JP, Brayne C, Aarsland D (2008) Dementia and survival in Parkinson disease: a 12-year population study. Neurology 70(13):1017\u20131022. https:\/\/doi.org\/10.1212\/01.wnl.0000306632.43729.24","journal-title":"Neurology"},{"issue":"3","key":"6897_CR5","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1152\/JN.00664.2009","volume":"103","author":"C Cho","year":"2010","unstructured":"Cho C, Kunin M, Kudo K, Osaki Y, Olanow CW, Cohen B, Raphan T (2010) Frequency-velocity mismatch: a fundamental abnormality in parkinsonian gait. J Neurophysiol 103(3):1478\u20131489. https:\/\/doi.org\/10.1152\/JN.00664.2009","journal-title":"J Neurophysiol"},{"issue":"7","key":"6897_CR6","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1007\/S40520-017-0838-0\/TABLES\/1","volume":"30","author":"N Ciccarelli","year":"2018","unstructured":"Ciccarelli N, Monaco MR, Lo, Fusco D, Vetrano DL, Zuccal\u00e0 G, Bernabei R, Brandi V, Pisciotta MS, Silveri MC (2018) The role of cognitive reserve in cognitive aging: what we can learn from Parkinson\u2019s disease. Aging Clin Exp Res 30(7):877\u2013880. https:\/\/doi.org\/10.1007\/S40520-017-0838-0\/TABLES\/1","journal-title":"Aging Clin Exp Res"},{"issue":"6","key":"6897_CR7","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1080\/016909696387042","volume":"11","author":"CM Connine","year":"1996","unstructured":"Connine CM, Titone D (1996) Phoneme monitoring. Lang Cogn Processes 11(6):635\u2013646. https:\/\/doi.org\/10.1080\/016909696387042","journal-title":"Lang Cogn Processes"},{"issue":"10","key":"6897_CR8","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1002\/MDS.26269","volume":"30","author":"C Curtze","year":"2015","unstructured":"Curtze C, Nutt JG, Carlson-Kuhta P, Mancini M, Horak FB (2015) Levodopa is a double-edged Sword for Balance and Gait in People with Parkinson\u2019s Disease. Mov Disord 30(10):1361\u20131370. https:\/\/doi.org\/10.1002\/MDS.26269","journal-title":"Mov Disord"},{"issue":"10","key":"6897_CR9","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1080\/09593985.2018.1551455","volume":"36","author":"TB De Freitas","year":"2020","unstructured":"De Freitas TB, Leite PHW, Don\u00e1 F, Pompeu JE, Swarowsky A, Torriani-Pasin C (2020) The effects of dual task gait and balance training in Parkinson\u2019s disease: a systematic review. Physiother Theory Pract 36(10):1088\u20131096. https:\/\/doi.org\/10.1080\/09593985.2018.1551455","journal-title":"Physiother Theory Pract"},{"issue":"2","key":"6897_CR10","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1111\/JNP.12028","volume":"7","author":"G Dirnberger","year":"2013","unstructured":"Dirnberger G, Jahanshahi M (2013) Executive dysfunction in Parkinson\u2019s disease: a review. J Neuropsychol 7(2):193\u2013224. https:\/\/doi.org\/10.1111\/JNP.12028","journal-title":"J Neuropsychol"},{"issue":"11","key":"6897_CR11","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1097\/PHM.0000000000000392","volume":"94","author":"H Fern\u00e1ndez-Lago","year":"2015","unstructured":"Fern\u00e1ndez-Lago H, Bello O, L\u00f3pez-Alonso V, S\u00e1nchez JA, Morenilla L, Fern\u00e1ndez-Del-Olmo M\u00c1 (2015) Gait Pattern and Cognitive Performance during Treadmill walking in Parkinson Disease. Am J Phys Med Rehabil 94(11):931\u2013940. https:\/\/doi.org\/10.1097\/PHM.0000000000000392","journal-title":"Am J Phys Med Rehabil"},{"issue":"3","key":"6897_CR12","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","volume":"12","author":"MF Folstein","year":"1975","unstructured":"Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189\u2013198. https:\/\/doi.org\/10.1016\/0022-3956(75)90026-6","journal-title":"J Psychiatr Res"},{"issue":"15","key":"6897_CR13","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1002\/MDS.22340","volume":"23","author":"CG Goetz","year":"2008","unstructured":"Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Zweig RM (2008) Movement Disorder Society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS): Scale presentation and clinimetric testing results. Mov Disord 23(15):2129\u20132170. https:\/\/doi.org\/10.1002\/MDS.22340","journal-title":"Mov Disord"},{"issue":"7","key":"6897_CR14","doi-asserted-by":"publisher","first-page":"4185","DOI":"10.1007\/S10072-022-05985-1","volume":"43","author":"L Gu","year":"2022","unstructured":"Gu L, Xu H (2022) Effect of cognitive reserve on cognitive function in Parkinson\u2019s disease. Neurol Sciences: Official J Italian Neurol Soc Italian Soc Clin Neurophysiol 43(7):4185\u20134192. https:\/\/doi.org\/10.1007\/S10072-022-05985-1","journal-title":"Neurol Sciences: Official J Italian Neurol Soc Italian Soc Clin Neurophysiol"},{"key":"6897_CR15","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/J.EXGER.2018.11.020","volume":"115","author":"S Guzzetti","year":"2019","unstructured":"Guzzetti S, Mancini F, Caporali A, Manfredi L, Daini R (2019) The association of cognitive reserve with motor and cognitive functions for different stages of Parkinson\u2019s disease. Exp Gerontol 115:79\u201387. https:\/\/doi.org\/10.1016\/J.EXGER.2018.11.020","journal-title":"Exp Gerontol"},{"issue":"5","key":"6897_CR16","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1080\/13803395.2013.798397","volume":"35","author":"CI Higginson","year":"2013","unstructured":"Higginson CI, Lanni K, Sigvardt KA, Disbrow EA (2013) The contribution of trail making to the prediction of performance-based instrumental activities of daily living in Parkinson\u2019s disease without dementia. J Clin Exp Neuropsychol 35(5):530\u2013539. https:\/\/doi.org\/10.1080\/13803395.2013.798397","journal-title":"J Clin Exp Neuropsychol"},{"issue":"3","key":"6897_CR17","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1136\/JNNP.55.3.181","volume":"55","author":"AJ Hughes","year":"1992","unstructured":"Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson\u2019s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55(3):181\u2013184. https:\/\/doi.org\/10.1136\/JNNP.55.3.181","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"4","key":"6897_CR18","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1177\/1545968321999053","volume":"35","author":"H Johansson","year":"2021","unstructured":"Johansson H, Ekman U, Rennie L, Peterson DS, Leavy B, Franz\u00e9n E (2021) Dual-Task effects during a motor-cognitive Task in Parkinson\u2019s Disease: patterns of prioritization and the influence of Cognitive Status. Neurorehabilit Neural Repair 35(4):356. https:\/\/doi.org\/10.1177\/1545968321999053","journal-title":"Neurorehabilit Neural Repair"},{"issue":"8","key":"6897_CR19","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1002\/MDS.26272","volume":"30","author":"V Kotagal","year":"2015","unstructured":"Kotagal V, Bohnen NI, M\u00fcller MLTM, Koeppe RA, Frey KA, Langa KM, Albin RL (2015) Educational Attainment and Motor Burden in Parkinson disease. Mov Disorders: Official J Mov Disorder Soc 30(8):1143. https:\/\/doi.org\/10.1002\/MDS.26272","journal-title":"Mov Disorders: Official J Mov Disorder Soc"},{"issue":"13","key":"6897_CR20","doi-asserted-by":"publisher","first-page":"2305","DOI":"10.1002\/MDS.23868","volume":"26","author":"A Kudlicka","year":"2011","unstructured":"Kudlicka A, Clare L, Hindle JV (2011) Executive functions in Parkinson\u2019s disease: systematic review and meta-analysis. Mov Disorders: Official J Mov Disorder Soc 26(13):2305\u20132315. https:\/\/doi.org\/10.1002\/MDS.23868","journal-title":"Mov Disorders: Official J Mov Disorder Soc"},{"issue":"4","key":"6897_CR21","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1111\/J.1532-5415.2005.53221.X","volume":"53","author":"ZS Nasreddine","year":"2005","unstructured":"Nasreddine ZS, Phillips NA, B\u00e9dirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H (2005) The Montreal Cognitive Assessment, MoCA: a brief Screening Tool for mild cognitive impairment. J Am Geriatr Soc 53(4):695\u2013699. https:\/\/doi.org\/10.1111\/J.1532-5415.2005.53221.X","journal-title":"J Am Geriatr Soc"},{"issue":"3","key":"6897_CR22","doi-asserted-by":"publisher","first-page":"218","DOI":"10.3275\/7800","volume":"24","author":"M Nucci","year":"2012","unstructured":"Nucci M, Mapelli D, Mondini S (2012) Cognitive Reserve Index questionnaire (CRIq): a new instrument for measuring cognitive reserve. Aging Clin Exp Res 24(3):218\u2013226. https:\/\/doi.org\/10.3275\/7800","journal-title":"Aging Clin Exp Res"},{"key":"6897_CR23","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/J.NEUROSCIENCE.2018.03.021","volume":"379","author":"AL Penko","year":"2018","unstructured":"Penko AL, Streicher MC, Koop MM, Dey T, Rosenfeldt AB, Bazyk AS, Alberts JL (2018) Dual-task interference disrupts Parkinson\u2019s Gait Across multiple cognitive domains. Neuroscience 379:375\u2013382. https:\/\/doi.org\/10.1016\/J.NEUROSCIENCE.2018.03.021","journal-title":"Neuroscience"},{"key":"6897_CR24","doi-asserted-by":"publisher","unstructured":"Plummer P, Eskes G (2015) Measuring treatment effects on dual-task performance: a framework for research and clinical practice. Front Hum Neurosci 9(APR). https:\/\/doi.org\/10.3389\/FNHUM.2015.00225","DOI":"10.3389\/FNHUM.2015.00225"},{"key":"6897_CR25","volume-title":"R: a Language and Environment for Statistical Computing","author":"R Core Team","year":"2023","unstructured":"R Core Team (2023) R: a Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna. https:\/\/www.r-project.org\/"},{"issue":"10","key":"6897_CR26","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.1016\/J.APMR.2004.01.025","volume":"85","author":"L Rochester","year":"2004","unstructured":"Rochester L, Hetherington V, Jones D, Nieuwboer A, Willems AM, Kwakkel G, Van Wegen E (2004) Attending to the task: interference effects of functional tasks on walking in Parkinson\u2019s disease and the roles of cognition, depression, fatigue, and balance. Arch Phys Med Rehabil 85(10):1578\u20131585. https:\/\/doi.org\/10.1016\/J.APMR.2004.01.025","journal-title":"Arch Phys Med Rehabil"},{"issue":"3","key":"6897_CR27","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1111\/JGS.17010","volume":"69","author":"R Sakurai","year":"2021","unstructured":"Sakurai R, Kim Y, Inagaki H, Tokumaru AM, Sakurai K, Shimoji K, Kitamura A, Watanabe Y, Shinkai S, Awata S (2021) MMSE Cutoff discriminates hippocampal atrophy: neural evidence for the cutoff of 24 points. J Am Geriatr Soc 69(3):839\u2013841. https:\/\/doi.org\/10.1111\/JGS.17010","journal-title":"J Am Geriatr Soc"},{"issue":"1\u20132","key":"6897_CR28","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1300\/J018V05N01_09","volume":"5","author":"JI Sheikh","year":"1986","unstructured":"Sheikh JI, Yesavage JA (1986) 9\/Geriatric Depression Scale (GDS). Clin Gerontologist 5(1\u20132):165\u2013173. https:\/\/doi.org\/10.1300\/J018V05N01_09","journal-title":"Clin Gerontologist"},{"issue":"10","key":"6897_CR29","doi-asserted-by":"publisher","first-page":"2015","DOI":"10.1016\/J.NEUROPSYCHOLOGIA.2009.03.004","volume":"47","author":"Y Stern","year":"2009","unstructured":"Stern Y (2009) Cognitive reserve. Neuropsychologia 47(10):2015\u20132028. https:\/\/doi.org\/10.1016\/J.NEUROPSYCHOLOGIA.2009.03.004","journal-title":"Neuropsychologia"},{"issue":"9","key":"6897_CR30","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1111\/J.1532-5415.1992.TB01992.X","volume":"40","author":"TN Tombaugh","year":"1992","unstructured":"Tombaugh TN, McIntyre NJ (1992) The mini-mental state examination: a comprehensive review. J Am Geriatr Soc 40(9):922\u2013935. https:\/\/doi.org\/10.1111\/J.1532-5415.1992.TB01992.X","journal-title":"J Am Geriatr Soc"},{"key":"6897_CR31","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/J.PARKRELDIS.2019.10.005","volume":"68","author":"J Wegrzyk","year":"2019","unstructured":"Wegrzyk J, Armand S, Chiuv\u00e9 SC, Burkhard PR, Allali G (2019) Education level affects dual-task gait after deep brain stimulation in Parkinson\u2019s disease. Parkinsonism Relat Disord 68:65\u201368. https:\/\/doi.org\/10.1016\/J.PARKRELDIS.2019.10.005","journal-title":"Parkinsonism Relat Disord"},{"issue":"2","key":"6897_CR32","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1007\/S00415-012-6683-3","volume":"260","author":"LB Wild","year":"2013","unstructured":"Wild LB, De Lima DB, Balardin JB, Rizzi L, Giacobbo BL, Oliveira HB, De Lima Argimon II, Peyr\u00e9-Tartaruga LA, Rieder CRM, Bromberg E (2013) Characterization of cognitive and motor performance during dual-tasking in healthy older adults and patients with Parkinson\u2019s disease. J Neurol 260(2):580\u2013589. https:\/\/doi.org\/10.1007\/S00415-012-6683-3","journal-title":"J Neurol"},{"key":"6897_CR33","doi-asserted-by":"publisher","unstructured":"World Medical Association (2013). World Medical Association Declaration of Helsinki: Ethical principles for medical research involving human subjects. JAMA, 310(20), 2191\u20132194. https:\/\/doi.org\/10.1001\/jama.2013.281053","DOI":"10.1001\/jama.2013.281053"}],"container-title":["Experimental Brain Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00221-024-06897-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00221-024-06897-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00221-024-06897-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T11:12:03Z","timestamp":1723029123000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00221-024-06897-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,25]]},"references-count":33,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2024,9]]}},"alternative-id":["6897"],"URL":"https:\/\/doi.org\/10.1007\/s00221-024-06897-6","relation":{},"ISSN":["0014-4819","1432-1106"],"issn-type":[{"value":"0014-4819","type":"print"},{"value":"1432-1106","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,25]]},"assertion":[{"value":"29 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 July 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was approved by the ethical committee of the University of A Coru\u00f1a (code: 2009\/346). All participants gave written informed consent following the declaration of Helsinki (World Medical Association, ) before entering the study. Registered Clinical Trial N\u00baISRCTN52284448.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}