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Persisting fatigue after infection may have a biological origin with psychological and social factors contributing to the disease phenotype. This is consistent with the biopsychosocial framework, which considers fatigue to be the result of a complex interaction between biological, psychological, and social factors. In line, similar manifestations of chronic fatigue are observed in chronic fatigue syndrome\/myalgic encephalomyelitis (CFS\/ME) and juvenile idiopathic arthritis (JIA). Cognitive behavioral therapy is often recommended as treatment for chronic fatigue, considering its effectiveness on the group level. However, not everybody benefits on the individual level. More treatment success at the individual level might be achieved with patient-tailored treatments that incorporate the biopsychosocial framework.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In addition to biological assessments of blood, stool, saliva, and hair, the QFS-study consists of a randomized controlled trial (RCT) in which a single-subject experimental case series (<jats:italic>N=1<\/jats:italic>) design will be implemented using Experience Sampling Methodology in fatigued adolescents and young adults with QFS, CFS\/ME, and JIA (aged 12\u201329). With the RCT design, the effectiveness of patient-tailored PROfeel lifestyle advices will be compared against generic dietary advices in reducing fatigue severity at the group level. Pre-post analyses will be conducted to determine relevance of intervention order. By means of the <jats:italic>N<\/jats:italic>=1 design, effectiveness of both advices will be measured at the individual level.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>The QFS-study is a comprehensive study exploring disrupted biological factors and patient-tailored lifestyle advices as intervention in adolescent and young adults with QFS and similar manifestations of chronic fatigue. Practical or operational issues are expected during the study, but can be overcome through innovative study design, statistical approaches, and recruitment strategies. Ultimately, the study aims to contribute to biological research and (personalized) treatment in QFS and similar manifestations of chronic fatigue.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>Trial NL8789. Registered July 21, 2020.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-022-06620-2","type":"journal-article","created":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T09:03:57Z","timestamp":1660899837000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Identifying disrupted biological factors and patient-tailored interventions for chronic fatigue in adolescents and young adults with Q-Fever Fatigue Syndrome, Chronic Fatigue Syndrome and Juvenile Idiopathic Arthritis (QFS-study): study protocol for a randomized controlled trial with single-subject experimental case series design"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7769-5459","authenticated-orcid":false,"given":"Anouk","family":"Vroegindeweij","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joost F.","family":"Swart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Houtveen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niels","family":"Eijkelkamp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elise M.","family":"van de Putte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nico M.","family":"Wulffraat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanne L.","family":"Nijhof","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"issue":"12","key":"6620_CR1","doi-asserted-by":"publisher","first-page":"953","DOI":"10.7326\/0003-4819-121-12-199412150-00009","volume":"121","author":"K Fukuda","year":"1994","unstructured":"Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. 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New York: Routledge; 2013.","edition":"2"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-022-06620-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-022-06620-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-022-06620-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T09:04:10Z","timestamp":1660899850000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-022-06620-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,19]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["6620"],"URL":"https:\/\/doi.org\/10.1186\/s13063-022-06620-2","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,19]]},"assertion":[{"value":"7 June 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 August 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The UMC Utrecht IRB reviewed and approved the QFS-study protocol titled \u201cA study focused at identifying disrupted biological factors and patient-tailored interventions for adolescents with Q-fever fatigue syndrome\u201d on June 16, 2020. IRB\u2019s reference number: 20\/166. Participants and their parents receive verbal and written information about the study and informed consent will be obtained from all participants before randomization. In case participants are under the age of 16, informed consent will be obtained from the participant and his\/her parents or legal guardians.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate\u00a0{24}"}},{"value":"It is possible to receive a model consent form from the corresponding author upon request.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication\u00a0{32}"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests\u00a0{28}"}}],"article-number":"683"}}